No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Maternal exposure to polystyrene nanoplastics causes brain abnormalities in progeny
Abstract
As global plastic production continues to grow, microplastics released from a massive quantity of plastic wastes have become a critical environmental concern. These microplastic particles are found in a wide range of living organisms in a diverse array of ecosystems. In this study, we investigated the biological effects of polystyrene nanoplastic (PSNP) on development of the central nervous system using cultured neural stem cells (NSCs) and mice exposed to PSNP during developmental stages. Our study demonstrates that maternal administration of PSNP during gestation and lactating periods altered the functioning of NSCs, neural cell compositions, and brain histology in progeny. Similarly, PSNP-induced molecular and functional defects were also observed in cultured NSCs in vitro. Finally, we show that the abnormal brain development caused by exposure to high concentrations of PSNP results in neurophysiological and cognitive deficits in a gender-specific manner. Our data demonstrate the possibility that exposure to high amounts of PSNP may increase the risk of neurodevelopmental defects.
... Various toxicological studies in animal and cell culture models have revealed that MNPs induced gastrointestinal toxicity (microbiota dysbiosis) (Li et al., 2020b), hepatotoxicity (Cheng et al., 2022;Shi et al., 2022), nephrotoxicity (Wang et al., 2023a;Huang et al., 2024a), neurotoxicity (Prust et al., 2020;Lee et al., 2022a;Liang et al., 2022;Wang et al., 2022a) and reproductive toxicity Li et al., 2021;Wei et al., 2022). However, MNPs can be transferred to F1 progeny through the placental barrier and mammary glands (Fournier et al., 2020;Jeong et al., 2022). Moreover, multiple studies have provided insights into the detrimental impacts of MNPs on the growth and development of organisms, especially during the early stages of development. ...
... Breast milk being the primary source of nutrition for infants, its contamination with MNPs could instigate oxidative stress and inflammatory responses causing acute or long-term developmental and metabolic disruptions (Ke et al., 2023;Saraluck et al., 2024). Furthermore, Jeong et al. (2022) have demonstrated the accumulation of PS-NP in the mammary glands of mice exposed during pregnancy day 8 to 18, which further gets transferred to offspring through breast milk after delivery. They concluded that MNPs translocated from mother to progeny only through breast milk, as there was no direct passage of particles to the embryos through the placenta . ...
... They concluded that MNPs translocated from mother to progeny only through breast milk, as there was no direct passage of particles to the embryos through the placenta . The lower permeability of the placental barrier could be due to the use of energy-intensive, active transport via ATP-binding cassette transporters, whereas the entry of medicines and compounds into breast milk relies solely on simple diffusion along a concentration gradient (Wanat, 2020;Jeong et al., 2022). Furthermore, the accumulation of PS-NP in the mammary glands of mice exposed during a gestational and lactational period can cause abnormal weight gain in the progeny due to altered lipid composition in maternal breast milk (Jeong et al., 2024). ...
... The outcome encompasses a cumulative total of 973 mice, divided into 3 developmental stages embryonic, young, and adult. Among these, 17 studies specifically used male mice, three studies were performed on females, three studies involved both genders [28,30,34], and only one study did not specify the gender used [27]. ...
... Conversely, two studies have noticed a reduced level of a specific microglia marker Iba1 [29], and decreased GFAP levels [32]. Interestingly, despite these pronounced effects, the progeny didn't reveal any inflammatory alterations in response to PS-MP/NP exposure [27,28,30]. ...
... Although maternal exposure to 1 mg/L of PS-MP/NP did not induce significant neuroinflammation in the offspring [27,30]. Liver exposure at 10 mg/L and 1 mg/L of PS-NP during gestation significantly upregulated the expression of Il-6, TNf-a, and Il-1b in mice offspring [74]. ...
... These small particles can also induce oxidative stress, inflammation, increased apoptosis, and even malignancy in the female reproductive system (Fig. 1). The transfer of NPs from the mother's body to the fetus can accumulate in their various tissues, including the brain, liver, lungs, kidneys, and heart, causing disturbances in metabolism, reproductive function, immune function, neural development, and cognitive function [77,78]. Also, maternal exposure to MNPs can cause transgenerational toxicity and premature death in children [49,79]. ...
... The passage of NPs through the blood-placenta barrier (BPB) and their transfer via breast milk to offspring are the two main pathways through which offspring are exposed to nanoplastic particles [29,78], and the transfer of these materials through the placenta depends on their size [164]. Exposure of mother mice to NPs during pregnancy and lactation can cause deposition of these nanoparticles in the intestine, liver, brain, lungs, kidney, and heart tissues of the next generation mice and disrupts their immune system, nervous system, metabolism, and reproduction [29,77,78]. ...
... The passage of NPs through the blood-placenta barrier (BPB) and their transfer via breast milk to offspring are the two main pathways through which offspring are exposed to nanoplastic particles [29,78], and the transfer of these materials through the placenta depends on their size [164]. Exposure of mother mice to NPs during pregnancy and lactation can cause deposition of these nanoparticles in the intestine, liver, brain, lungs, kidney, and heart tissues of the next generation mice and disrupts their immune system, nervous system, metabolism, and reproduction [29,77,78]. ...
The female reproductive system can face serious disorders and show reproductive abnormalities under the influence of environmental pollutants. Microplastics (MPs) and nanoplastics (NPs) as emerging pollutants, by affecting different components of this system, may make female fertility a serious challenge. Animal studies have demonstrated that exposure to these substances weakens the function of ovaries and causes a decrease in ovarian reserve capacity. Also, continuous exposure to micro/nano plastics (MNPs) leads to increased levels of reactive oxygen species, induction of oxidative stress, inflammatory responses, apoptosis of granulosa cells, and reduction of the number of ovarian follicles. Furthermore, by interfering with the hypothalamic-pituitary-ovarian axis, these particles disturb the normal levels of ovarian androgens and endocrine balance and delay the growth of gonads. Exposure to MNPs can accelerate carcinogenesis in the female reproductive system in humans and animal models. Animal studies have determined that these particles can accumulate in the placenta, causing metabolic changes, disrupting the development of the fetus, and endangering the health of future generations. In humans, the presence of micro/nanoplastics in placenta tissue, infant feces, and breast milk has been reported. These particles can directly affect the health of the mother and fetus, increasing the risk of premature birth and other pregnancy complications. This review aims to outline the hazardous effects of micro/nano plastics on female reproductive health and fetal growth and discuss the results of animal experiments and human research focusing on cellular and molecular pathways.
... Under pathological conditions, short-term exposure to reasonable microplastic concentrations is of greater practical significance. Literature suggests that daily microplastic exposure for a 60 kg person ranges from 0.17 to 1113.50 mg/kg (Cox et al., 2019;Jeong et al., 2022). This experiment simulates the human exposure level of 300 mg / kg. ...
... Based on the results of pyrolysis gas chromatography mass spectrometry analysis, polyethylene and polyvinyl chloride microplastics were detected in carotid artery plaques, with mean values of 21.7 ± 24.5 and 5.2 ± 2.4 μg /mg, respectively (Giovannucci et al., 2010). According to the literature, the dosage of microplastics ingested by humans is approximately 0.1-5 g per week (Jeong et al., 2022;Senathirajah et al., 2021). As the global plastic production increases, the amount of microplastic contaminants released into the environment has been continuously soaring. ...
Diabetes has become a global health crisis, affecting over 800 million people, with serious complications such as vascular and neurological damage. While diabetes management has been extensively studied, the impact of environmental pollutants, particularly microplastics (PS), on diabetic health remains poorly understood. PS, defined as plastic particles smaller than 5 mm, are pervasive and can enter the body through inhalation or ingestion, posing potential risks. However, the effects of PS exposure, particularly in diabetes, have not been adequately explored. Most studies focus on high-concentration, long-term exposure, which does not reflect typical human exposure levels. This study investigates the effects of short-term PS exposure on diabetic SD rats, using histological, apoptotic, and omics techniques, including metabolomics, lipidomics, and 16S rDNA sequencing. Our results show that short-term PS exposure exacerbates lung and intestinal damage in diabetic rats, with significant alterations in the gut microbiome. We also observed correlations between differential metabolites and microbiota changes. These findings provide novel evidence that short-term PS exposure, at concentrations reflecting daily contact, worsens metabolic dysfunction and intestinal dysbiosis in diabetes. This study emphasizes the need to consider environmental pollutants in diabetes management and highlights potential strategies for prevention and therapy.
... Early-life exposures can occur during the prenatal period, but also postnatally when certain organ systems are still developing [37][38][39]. To date, studies involving exposure to sub-micron plastics have predominantly used well-characterized polystyrene (PS) particles [40][41][42][43][44][45][46][47][48][49][50][51][52]. For example, pulmonary exposure of pregnant Sprague Dawley rats to PS NPs (rhodaminelabeled, 20 nm) resulted in the translocation of particles to fetal and placental tissues [46]. ...
... For example, pulmonary exposure of pregnant Sprague Dawley rats to PS NPs (rhodaminelabeled, 20 nm) resulted in the translocation of particles to fetal and placental tissues [46]. In another study, the oral administration of PS NPs to pregnant mice resulted in the progeny exhibiting neurophysiological abnormalities and cognitive impairment in a gender-specific manner [49]. The exposure of adult mice to PS NPs (80 nm) during pregnancy showed sex-specific intestinal toxicity in the offspring [51]. ...
A critical knowledge gap currently exists regarding the potential risks of exposure to nanoplastics (NPs), particularly early in life during key stages of growth and development. Globally abundant plastics, polyamide (nylon) and polystyrene (PS), exist in various products and have been detected in food and beverages as small-scale plastics. In this study, we evaluated how early-life exposure to NPs affects key biological metrics in rat pups. Male and female animals received an oral dose (20 mg/kg/day) of nylon-11 NPs (114 ± 2 nm) or PS NPs (85 ± 1 nm) between postnatal day (PND) 7 and 10. The results showed slight differences in the ratio of liver weight to body weight for male rat pups exposed to PS NPs. Cardiac performance and levels of neurotransmitters and related metabolites in brain tissue showed no differences between animals exposed to NPs and controls. The endogenous metabolite profile in plasma was altered by oral administration of NPs, suggesting perturbation of metabolic pathways involved in amino acid and lipid metabolism. This study explored the biological impacts of oral NP exposure early in life, supporting the need for continued investigations into the potential health effects from exposure to NPs.
... PS-NPs administered via gavage during the gestation and lactation period were found to disrupt the structural integrity and neuronal composition of the developing brain, leading to functional impairments in hippocampal neural stem cells (NSCs) [46]. The study further demonstrated that aberrant brain development leads to neurophysiological and cognitive deficits, with these impairments manifesting in a sex-dependent manner [46]. ...
... PS-NPs administered via gavage during the gestation and lactation period were found to disrupt the structural integrity and neuronal composition of the developing brain, leading to functional impairments in hippocampal neural stem cells (NSCs) [46]. The study further demonstrated that aberrant brain development leads to neurophysiological and cognitive deficits, with these impairments manifesting in a sex-dependent manner [46]. Studies have also found that maternal exposure to PS-NPs can reduce the expression of neurodevelopmental proteins and an increase in inhibitory proteins in the hippocampus, which is crucial for learning and memory [47]. ...
Micro(nano)plastics (MNPs) pose a significant threat to both ecological environments and human health. This review systematically examines the developmental toxicity of MNPs in mammals, with a particular focus on the impact of maternal and paternal exposure on offspring. Evidence indicates that MNPs can cross placental barriers, inducing abnormal development of embryos, fetuses, and placentas. This disruption leads to a range of adverse outcomes, including neurodevelopmental abnormalities, behavioral disorders, reproductive system damage, etc., in offspring. Through a comprehensive analysis of the existing literature, this review aims to provide a foundation for future research on the developmental toxicity of MNPs and highlight the urgent need for action to mitigate the detrimental effects of MNPs on human health and ecosystem integrity.
... In this context, it has been shown that maternal exposure to MPs during gestation results in its translocation to placenta and fetal tissues (Cary et al. 2023), significantly affecting the metabolism of the pregnant mother (Luo et al. 2019), reducing the placental weight and efficiency, and increasing the number of resorption sites (Cary et al. 2023;Bai et al. 2024). Several deleterious effects on fetuses from mothers exposed to MPs during gestation have also been reported in recent studies, such as growth restriction, an increase in malformations, and an alteration of metabolism (Luo et al. 2019;Aghaei et al. 2022;Jeong et al. 2022). In the majority of experimental studies, polystyrene (PS-MPs) was used as MPs and the most harmful effects were often obtained following the use of particles with a diameter of 5 µm or less (Luo et al. 2019). ...
Although the presence of microplastics (MPs) in the placenta of mammals and their toxicity are currently well proven, the mechanism of their translocation across the maternal–fetal barrier has not been completely uncovered. We hypothesize that the translocation of MPs and their toxic effects partly involve the alteration of the placental barrier permeability. For this purpose, the effects of realistic concentration of human exposure (0.1 mg/kg) of spherical polystyrene microplastics (PS-MPs) with a diameter of 5 µm were assessed in female rat during pregnancy, focusing on tissue expression changes of ion channels and junction proteins as markers of placental barrier permeability. The toxicity of PS-MPs, accumulated mainly in the labyrinth zone (LZ), was manifested by some histological alterations of the placental tissue, notably the reduction of the LZ thickness, the disturbance of the oxidative status, and by the apoptosis induction. In addition, exposure to PS-MPs affected placental barrier permeability by reducing gap junction (CX43) and tight junction (ZO1, Claudin 3, and Claudin 4) protein expression as well as by changes in the expression pattern of placental ion transporters with a significant decrease of Na⁺/K⁺-ATPase expression versus an increase in that of Na–K–Cl cotransporter. Overall, these findings confirmed the direct toxic effects of PS-MPs on placental tissue and demonstrated, for the first time, that realistic concentrations of human exposure to MPs adversely affected placental barrier permeability in pregnant rats.
... Another 12 studies [71,80,83,85,95,110,114,123,125,139,155,160] involving 10 different cell lines (murine HT22, BV2, human hCMED/D3, murine C17.2 and primary hippocampal NSCs, fish cell lines DLB-1 and Fub-1, and human SH-SY5Y and hNS1) assessed the nervous system. Again, uPS negatively affected cell viability in 78% of studies and induced apoptosis in 33%. ...
Nanoplastic (NP) pollution has emerged as a growing concern due to its potential impact on human health, although its adverse effects on different organ systems are not yet fully understood. This systematic scoping review, conducted in accordance with international guidelines, aimed to map the current evidence on the biological effects of NPs. In vitro animal studies assessing cellular damage caused by exposure to any type of NP were searched on PubMed, Web of Science, and Scopus. Data on primary outcomes related to genotoxicity and cytotoxicity (cell viability, oxidative stress, inflammation, DNA and cytoplasmic damage, apoptosis) were extracted from the included studies, and overall reporting quality was assessed. A total of 108 articles published between 2018 and 2024, mostly by China (54%), Spain (14%), and Italy (9%), were included. Polystyrene (PS) was the most frequently studied polymer (85%). NP sizes in solution ranged from 15 to 531 nm, with a higher prevalence in the 40–100 nm range (38%). The overall quality of studies was rated as moderate (60%), with many lacking essential details about cell culture conditions (e.g., pH of the medium, passage number, substances used). A higher frequency of negative effects from NP exposure was observed in respiratory cell lines, while immune, digestive, and hepatic cell lines showed greater resistance. Nervous, urinary, and connective tissue systems were impacted by NPs. Positively charged and smaller PS particles were consistently associated with higher toxicity across all systems. In summary, this review highlights the multifactorial nature of NP toxicity, influenced by size, surface charge, and polymer type. It also reveals a significant knowledge gap, stemming from the predominant use of immortalized monocultures exposed to commercially available PS NPs, the limited use of environmentally relevant particles, and the underutilization of advanced experimental models (e.g., organ-on-chip systems) that better mimic physiological conditions.
... mg of NPs in mice [31]. Exposure to high doses of NPs (≥ 500 µg/d) can significantly affect brain function [32]. For instance, administering 100 nm PS-NPs at a dose of 1 mg/d via gavage for 28 d resulted in anxiety and depression [33]. ...
Background
Recent studies emphasize the significance of copper dyshomeostasis in neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, thereby highlighting the role of copper in neurotoxicity. Cuproptosis, a novel mechanism of copper-dependent cell death, remains underexplored, particularly concerning environmental pollutants like polystyrene nanoplastics (PS-NPs). While PS-NPs are recognized for inducing neurotoxicity through various forms of cell death, including apoptosis and ferroptosis, their potential to trigger neuronal cuproptosis has not yet been investigated. This study aims to determine whether exposure to PS-NPs induces neurotoxicity via cuproptosis and to explore the preliminary molecular mechanisms involved, thereby addressing this significant knowledge gap.
Methods
Seven-week-old male C57BL/6 mice were exposed to PS-NPs at dose of 12.5 mg/kg, and were co-treated with the antioxidant N-acetylcysteine (NAC). Complementary in vitro experiments were conducted using SH-SY5Y neuronal cells exposed to PS-NPs at a concentration of 0.75 mg/mL, with interventions that included the copper chelator tetrathiomolybdate (TTM), NAC, and the MAPK inhibitor PD98059.
Results
Exposure to PS-NPs significantly increased cerebral copper accumulation (P < 0.05) and induced cuproptosis, characterized by lipid-acylated DLAT oligomerization, dysregulation of cuproptosis regulators (FDX1, LIAS, HSP70), and mitochondrial damage. In murine models, PS-NPs elicited neurotoxicity, as evidenced by neuronal loss, decreased Nissl body density, impaired synaptic plasticity, and suppressed oxidative stress markers (GSH, SOD, Nrf2), alongside activation of the ERK-MAPK pathway, ultimately resulting in deficits in learning and memory. Treatment with NAC alleviated these adverse effects. In SH-SY5Y cells, exposure to PS-NPs resulted in reduced cell viability (p < 0.01), an effect that was mitigated by TTM. Furthermore, NAC and PD98059 were found to reverse elevated copper levels, cuproptosis markers, and mitochondrial anomalies (p < 0.05).
Conclusion
This study presents preliminary evidence indicating that PS-NPs may induce neuronal cuproptosis, potentially through the oxidative stress-mediated activation of the ERK-MAPK pathway, which contributes to cognitive dysfunction in mice. These findings provide insights into the potential mechanisms underlying PS-NPs neurotoxicity and highlight possible therapeutic targets, such as copper chelation or MAPK inhibition, for mitigating the neurological risks associated with nanoplastic exposure, pending further validation in human-relevant models.
... Recent studies have reported microplastic particles in the human placenta, suggesting that these contaminants can enter the maternal body through ingestion, skin contact, and inhalation, ultimately crossing the placenta and reaching the amniotic fluid and fetus [19,20]. Although high-quality observational studies are needed to fully understand the effects of prenatal microplastic exposure, research indicates that such exposure during pregnancy and early life may lead to lasting changes in the reproductive and central nervous systems across species [21][22][23]. Similarly, infants born to mothers exposed to toxicants, including pesticides or industrial chemicals mobilized by extreme weather events, may face risks of altered immune responses and developmental issues, particularly in the respiratory, reproductive, and nervous systems [24]. ...
Climate change significantly impacts child health, with Brazilian children facing unique vulnerabilities due to the country’s environmental and socioeconomic landscape. This article explores how rising temperatures, pollution, and extreme weather amplify respiratory, neurological, and psychological issues, spread vector-borne diseases, and reduce food security, disproportionately impacting children and adolescents. We also discuss mitigation strategies and recommendations for climate adaptation, including initiatives for sustainable land-use, expanded educational and health programs, and enhanced support for biodiversity conservation. These actions are essential to safeguarding child health and addressing the growing climate crisis nationally and internationally.
... Importantly, MPs/NPs and the compounds they contain can act as endocrine disruptors, altering normal functions of the endocrine system and causing damage to the entire organism, its progeny, or to a specific cell population of the organism itself (Lim, 2021). Animal studies confirmed the toxic effects of plastic particles on offspring generation, which interfere with cellular energy production and lipid metabolisms, leading to oxidative stress and neurotoxic response, suggesting mitochondrial dysfunctions (Jeong et al., 2022). ...
Background
In the human placenta, we have detected the MPs by Raman microspectroscopy analysis and, for the first time, with transmission electron microscopy. MPs fragments have been localized in different compartments of placental tissue, free in the cytoplasm and within organelles like lysosomes. Moreover, their presence has been correlated with ultrastructural alterations of some cell organelles, typical of metabolic stress, mainly dilated rough endoplasmic reticulum and numerous swollen electrodense mitochondria, as well as signs derived from involuting organelles. As a result, we have speculated that microplastics in the placenta could be responsible for pathological traits activation such as oxidative stress, apoptosis, and inflammation causing long-term effects on the health of the mother and child. To demonstrate the cytotoxicity of PS-NPs on the placenta and confirm the in vivo results, we performed in vitro experiments on a trophoblast human cell line, the HTR8/SVneo cells.
Materials and Methods
HTR8/SVneo cells were treated, for 24 h and 48h, with increasing concentrations (10, 25, 50, 75, and 100 μg/mL) of 0.05 µm polystyrene (PS) and cellular viability was evaluated by Counting Kit-8. Fluorescent PS-NPs examined under fluorescence/confocal microscopy were used to investigate the internalization of plastics in the placenta cells. Transmission electron microscopy was used to evaluate possible PS-NPs-dependent ultrastructural alterations of cells and organelles.
Results
Our study shows that starting from 24 h exposure, PS-NPs treatment, at 50 μg/mL dose, has a cytotoxic effect on placental cells, causing the death of 40% of cells and affecting the morphology of the surviving cells. In addition, PS-NPs alter the ultrastructure of some organelles in the surviving cells, like those we have already described in vivo. We found that NPs enter the cells, affecting the endoplasmic reticulum and mitochondria morphology, accumulating as aggregates within lysosome-like organelles. Interestingly these aggregates become larger as the concentration of NPs increases. We speculated that the accumulation of NPs inside lysosome-like organelles could result from a prolonged and impossible attempt by the cell to remove and destroy PS. This would lead to ER and mitochondrial stress, impairing mitochondria/ER functions and oxidative stress, thus activating the apoptotic pathway and suggesting that PS-NPs could act as a cell stressor, leading to the death of cells. In support of our hypothesis, we also found NPs associated with morphological signs of cellular regression and degeneration, such as the presence of a highly vacuolized cytoplasm, dilatation, and vesiculation of ER, associated with the uncoupling/loss of associated mitochondria, cytoplasmic fragments, and free organelles deriving from cellular lysis.
Conclusion
Based on electron microscopy and immunofluorescence analysis and in vitro study, we demonstrate the cytotoxicity of PS-NPs in trophoblast cells together with ultrastructural alterations associated with cellular regression and degeneration typical of metabolic stress. An abnormal amount of NPs in the cells might determine a persistent cellular alarm CDR (cell danger response), the evolutionarily conserved metabolic response that protects the cells and hosts from harm triggered by chemical (as in the case of NPs/MPs), physical, or biological agents that exceed the cellular capacity for homeostasis. This in vitro study could further help to demonstrate that the inevitable exposure of MPs/NPs in the environment, which characterizes the modern world, might be partially responsible for the epidemic of non-transmissible disease.
... This does not constitute a representative model for studying the effects of realistic exposure to MP/NP. Other studies have evaluated MP/NP exposure on gestational mouse model and suggest an increased fetal resorption rate, a lower birth weight associated to fetoplacental hypoperfusion and fetal growth restriction [30,32,33] as well as alterations in offspring metabolism and cerebral development [34][35][36][37]. In humans, MP-NP are suspected to be involved in the occurrence of intra-uterine growth retardation [12]. ...
... These disruptions impair the transmission of electrical signals and compromise the structural integrity of nerve cells [36]. As a result, microplastics can adversely affect the health and function of nerve cells, exacerbating cognitive impairment and increasing the risk of neurodegenerative diseases [37]. In conclusion, this study aims to explore the multiple impacts of microplastics on marine ecosystems and human health. ...
Brain ischemia, a condition in which the brain is deprived of blood flow, can lead to a stroke due to blocked or unstable blood vessels. Global cerebral ischemia (GCI), characterized by an interruption in blood flow, deprives the brain of oxygen and nutrients, producing reactive oxygen species (ROS) that trigger cell death, which kills nerve cells. Microplastics (MPs), tiny environmental pollutants, can enter the human body through contaminated food, water, disposable items, cosmetics, and more. Once in the brain, MPs can increase neuroinflammation by overstimulating inflammatory factors such as microglia. MPs can also damage neurons by scratching myelin and microtubules, slowing signal transduction, causing cognitive impairment, and leading to neuronal death. Furthermore, microtubule damage may result in the release of phosphorylated tau proteins, potentially linked to Alzheimer’s disease. We hypothesized that MPs could exacerbate neuroinflammation and microtubule destruction after GCI, leading to increased neuronal death. To test this hypothesis, we administered MPs (0.5 µm) orally at a dose of 50 mg/kg before and after inducing GCI. Staining techniques such as Fluoro-Jade B (FJB), ionized calcium-binding adaptor molecule 1 (Iba-1), cluster of differentiation 68 (CD68), myelin basic protein (MBP), and microtubule-associated protein 2 (MAP2) were used, along with Western blot analysis for interleukin-6 (IL-6), TNF-α, tau-5, and phospho-tau (S396) to evaluate the effects of MPs on neuronal cell death, neuroinflammation, and microtubule destruction. The results showed that MP accumulation significantly increased neuroinflammation, microtubule disruption, and neuronal cell death in the GCI-MP group compared to the GCI-vehicle group. Therefore, this study suggests that MP accumulation in daily life may contribute to the exacerbation of the disease, potentially leading to severe neuronal cell death after GCI.
... The increased ROS production accompanying high-fat diets can lead to lipid accumulation andimpairt mitochondrial function and dynamics [110,111]. MNPs have been found to induce similar mitochondrial dysfunction, with increased ROS production as a main mechanism for MNP-induced toxicity [112,113] (Figure 2). The combination of these stressors-HFD and MNPs-places a dual burden on mitochondria where excessive ROS production overwhelms their capacity to meet cellular energy demands. ...
Pollution by emerging contaminants, such as micro-nanoplastics, alongside the exponential prevalence of diet-related diseases like obesity and type 2 diabetes, poses significant concerns for modern societies. There is an urgent need to explore the synergistic effects of these two factors, as unhealthy lifestyles may increase disease susceptibility and amplify the harmful impacts of pollutants on human health. Mitochondria play a crucial role in both micro-nanoplastic-induced toxicity and in the pathogenesis of obesity and type 2 diabetes. This makes them a potential target for assessing the combined effects of micro-nanoplastic exposure and poor dietary habits. To address this issue, we conducted a review of the latest investigations evaluating the effects of micro-nanoplastics in the presence of unhealthy diets. Although the evidence is limited, the reviewed studies indicate that these particles may exacerbate common metabolic disturbances associated with obesity and type 2 diabetes: elevated fasting blood glucose and insulin levels, glucose intolerance, and insulin resistance. Some studies have identified mitochondrial dysfunction as a potential underlying mechanism driving these effects. Thus, mitochondria appear to be a key link between micro-nanoplastic exposure and diet-related diseases. Assessing the function of this organelle may allow a more fitted risk assessment of the potential impacts of micro-nanoplastics.
... Research has increasingly focused on the health impacts of MPs on various organisms, with studies frequently utilizing model species like zebrafish (Danio rerio), mice (Mus musculus), and rats (Rattus norvegicus) [8]. Studies in mice have documented increased oxidative stress and decreased energy metabolism following MP exposure [9,10]. Multiple studies have demonstrated that MP exposure in animal models leads to significant reproductive disruptions, including decreased sperm quality, altered testosterone levels, and damage to testicular tissues [11][12][13][14][15][16][17]. ...
Aim: Microplastics (MPs), widespread environmental contaminants, pose a growing risk to livestock and other animals by potentially polluting their feed and ecosystems. This study aims to investigate the impact of MP exposure on oxidative stress, testicular function , and androgen receptor gene expression in mice, providing insights into the potential reproductive health risks for animals. Methods: Adult male mice were divided into three groups: a control group and two groups exposed to polystyrene microplastics (PS-MPs) at concentrations of 0.1 mg/0.5 mL and 0.2 mg/1 mL, respectively. We evaluated antioxidant enzyme levels (catalase, super-oxide dismutase, peroxidase), reactive oxygen species (ROS) levels in testicular tissue, sperm count, viability, and motility, as well as histological changes in the testicular tissue. Furthermore, the gene expression levels of AR were assessed using qRT-PCR. Results: Exposure to PS-MPs led to a dose-dependent decrease in antioxidant enzyme levels and an increase in ROS levels in the testicular tissue. Similarly, sperm count, viability, and motility were significantly reduced in the PS-MPs-treated groups. Histological examinations revealed a noticeable adverse effects on testicular development, with a marked reduction in germ cell populations. The analysis of gene expression showed significant downregulation of AR genes in mice exposed to PS-MPs, indicating the potential endo-crine-disrupting effects of MP exposure. Conclusion: This study reveals that polystyrene MP exposure causes oxidative stress and reproductive damage in mice. These findings highlight the potential risks for livestock and other animals through contaminated feed, emphasizing the need for further research on MPs impact on animal health in agricultural ecosystems. Contact Md. Sadequl Islam sadequl@tch.hstu.ac.
Human exposure to micro- and nanoplastic (MNP) has become an increasing concern due to its accumulation in the environment and human body. In the human organism, MNP accumulates in various tissues, including the central nervous system, where it is associated which neurotoxic effects. Beyond its inherent toxicity, MNP also acts as a carrier for various chemical contaminants, including metals. Consequently, recent studies emphasize the importance of the evaluation of co-exposure scenarios involving MNP and other types of nanoparticles. In this study, we investigated effects of co-exposure to 20 nm silver nanoparticles (AgNPs) and 20 nm polystyrene nanoparticles (PSNPs) on cell viability and the expression of inflammation-related long non-coding RNAs (lncRNAs) in undifferentiated and differentiated Lund human mesencephalic (LUHMES) cells. While PSNPs alone did not significantly affect cell viability or lncRNA expression, AgNPs markedly reduced viability and deregulated lncRNA expression in both cell types. Notably, in differentiated cells, co-exposure to AgNPs and high concentrations of PSNPs led to a significantly greater reduction in viability compared to AgNPs alone, suggesting a synergistic effect. At the molecular level, both synergistic and antagonistic interactions between AgNPs and PSNPs were observed in the regulation of lncRNA expression, depending on the cell differentiation status. These findings highlight the complex biological interactions between AgNPs and PSNPs and emphasize the importance of considering nanoparticle co-exposures in toxicological evaluations, as combined exposures may significantly affect cellular and molecular responses.
There is a big need to restitute the agricultural soils. Consequences of decisions taken in the past, have given fingerprints in the agricultural sites. Among those fingerprints are the micro and nanoplastics. In the last decades, investigations of the presence and impact of micro/nanoplastics have been carried out in the agricultural soils. Polypropylene and polyethylene are the main plastic polymers prevailing in the agricultural soils, and there is awareness that agricultural soils are sink and source of micro and nanoplastics. The main aim of this short review is to demonstrate which is the impact of nanoplastics in the agricultural sites. For that, using the searching Scopus platform, a selection of papers has been carried out, where the words nanoplastics and agricultural sites were together, and the production of papers increases exponentially in the last years, having a total of 73 papers since 2017 to 2023. And most of the investigations have been performed in Asia. The impact of nanoplastics is recognized at the morphological, oxidative stress and genotoxicity on plants. Soil bacteria might shift their activities if micro/nanoplastics are present in soils. The gut bacteria microbiome diversity of earthworms is modified if soil micro/nanoplastics are present. The type of plastic, concentration and time of exposure play an important role on the impact that micro/nanoplastics might produce on plants, and soil organisms. It is evident that more studies are required since the agricultural soil is polluted with plastic debris. Human health relies on soil health. Therefore, the need of enhancing healthy soils, for healthy food and healthy humans.
The development of the brain is a highly coordinated process that begins early in gestation and relies on intricate interactions between maternal and fetal immune systems. Disruptions to this delicate prenatal immune environment can significantly impact fetal brain development, increasing the risk of a spectrum of neurological and behavioral disorders, including autism spectrum disorder (ASD), schizophrenia, depression, and anxiety. While maternal exposure to viral and bacterial infections has been extensively studied as a driver of these disruptions, emerging research highlights the potential role of non-infectious exposures—such as drugs of abuse and environmental contaminants—in shaping neurodevelopmental outcomes. This issue has gained urgency with the rising prevalence of neurodevelopmental disorders; in the United States, for instance, ASD diagnoses have surged from 1 in 150 children in the early 2000s to 1 in 36 by 2020. Within this context, the increasing detection of cannabis, micro- and nanoplastics (MPs/NPs), and flame retardants in maternal and fetal tissues warrants close scrutiny. These substances, which are growing in prevalence due to changing societal norms, widespread environmental pollution, and industrial practices, may disrupt neurodevelopment through immune-mediated mechanisms. Cannabis use during pregnancy, for example, has increased significantly with legalization, while MPs/NPs and flame retardants are now frequently detected in maternal blood, placenta, and breast milk, raising concerns about their impacts on fetal health. In this chapter, we summarize human and preclinical evidence to explore how perinatal exposure to these substances may alter neurodevelopment by disrupting maternal and/or fetal immunity. We begin with an overview of central nervous system development and the critical role of immune interactions in ensuring a healthy pregnancy. We then review evidence linking perinatal exposure to cannabis, MPs/NPs, and flame retardants to neurodevelopmental outcomes, emphasizing immune-mediated pathways such as alterations in cytokine production, microglial activation, and adaptive immune cell function. Finally, we identify key gaps in the literature and propose future research directions to better understand the complex interplay between environmental exposures, immune dysregulation, and neurodevelopmental outcomes.
Perinatal exposure to of cannabis, micro- and nanoplastics (MPs/NPs), and flame retardants may alter neurodevelopment by disrupting maternal and/or fetal immunity
Microplastics (MP; particles < 5 mm) have emerged as contaminants of growing ecotoxicological concern in aquatic environments and are a potential threat to human health. Notably, the use of MPs markedly increased during and after the corona virus disease 2019 pandemic due to the heightened emphasis on personal hygiene and sanitation.
Although research on MPs has intensified globally, conflicting results have led to ongoing debates and uncertainty regarding the effects of MPs on human organs and overall health.
Smaller particles are of particular concern because of their increased toxicity and ability to penetrate deeply into human tissues and organs. Additionally, irregularly shaped and fragmented MPs, which are prevalent in natural environments, pose greater risks. Irregular shapes facilitate tissue penetration and promote oxidative stress, thereby exacerbating toxic effects.
To better understand the effects of MPs on the human body, their effects on each organ or disease state should be categorized according to MP type, size, and shape. This approach provides valuable insights into the relationship between MPs and human health, thereby enabling informed discussions on the consumption and application of plastic products to promote future healthier living.
In this review, we discuss how MP size and shape influences their effects on human health. Furthermore, we categorize the most commonly used plastics as polystyrene, polypropylene, and polyethylene, thereby highlighting the specific effects of MPs derived from each category.
The usage of plastics in life and industrial applications has led to global environmental pollution by micro- and nanoplastics (MPs/NPs). Despite their widespread occurrence in the environment, little is known about their presence in humans and the potential implications for human health, particularly maternal and fetal health during the prenatal and neonatal periods. Studies on experimental animals indicate that exposure to MPs/NPs can lead to neurological abnormalities in offspring and hemodynamic alterations in the placenta and fetal cerebral arteries. These findings underscore the need for further epidemiological studies that examine the effects of MPs/NPs on fetal health during pregnancy, a critical period for neurological development. This review summarizes the existing knowledge on the effects of prenatal exposure to MPs/NPs on fetal development and birth outcomes in humans and provides a detailed overview of the challenges encountered in contamination prevention, quality assurance and quality control in analytical procedures. It also discusses the sampling and digestion methods used for the extraction of MPs/NPs from biological samples of maternal and fetal origin, highlighting the difficulties associated with accurately quantifying these particles in complex biological matrices, identifying the gaps in current research, and suggesting recommendations to improve methodologies for assessing the risks associated with prenatal MP/NP exposure.
Microplastics (MP) are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression. In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.
The scale of plastic pollution boggles the mind. Nearly 400 megatons of virgin plastics are produced annually, with an environmental release rate of 80%, and plastic waste, including microplastics and nanoplastics, is associated with a plethora of problems. The naturally evolved abilities of plastic-degrading microbes offer a starting point for generating sustainable and eco-centric solutions to plastic pollution—a field of endeavor we term eco-microbiology. Here, we developed an iterative discovery procedure coupling faster polyethylene terephthalate (PET)-dependent bioactivity screens with longer-term PET biodegradation assays to find biochemical boosters of PET consumption by the bacterium Piscinibacter sakaiensis. We discovered multiple hits supporting the enhancement of PET biodegradation, with a 0.39% dilution of growth medium #802, a rich medium similar to Luria-Bertani broth, on average more than doubling the rate of PET biodegradation both alone and in combination with 0.125% ethylene glycol. In addition, we identified other chemical species (sodium phosphate, L-serine, GABA) worth further exploring, especially in combination with growth medium #802, for enhanced PET biodegradation by P. sakaiensis. This work represents an important step toward the creation of a low-cost PET fermentation process needed to help solve PET plastic pollution.
IMPORTANCE
Plastic pollution is an urgent issue. Adding to the well-known problems of bulk plastic litter, shed microplastics and nanoplastics are globally distributed, found in diverse organisms including human foodstuffs and tissues, and increasingly associated with chronic disease. Solutions are needed and the microbial world offers abundant help via naturally evolved consumers of plastic waste. We are working to accelerate polyethylene terephthalate (PET) plastic biodegradation by Piscinibacter sakaiensis, a recently described bacterium that evolved to slowly but completely consume PET, one of the most common types of plastic pollution. We used a combination of PET-dependent bioactivity screens and biodegradation tests to find stimulators of PET biodegradation. Out of hundreds, we found a small number of biochemical conditions that more than double the PET biodegradation rate. Our work provides a foundation for further studies to realize a fermentation process needed to help solve PET plastic pollution.
The increasing accumulation of plastics in the environment has raised concerns regarding their potential health hazards.
Nano-plastics (NPs), defined as particles smaller than 1 µm, have emerged as a significant environmental contaminant due to their potential ecological impacts. This study explores the size-dependent dynamics and tissue-specific distribution of polystyrene nano-plastics (PS-NPs) in Danio rerio exposed to PS-NPs at an environmentally relevant concentration of 1 μg/mL for 28 days, followed by a 17-day depuration period. PS-NPs of 20, 100, 200, and 500 nm were assessed in the intestine, liver, gills, muscle, and brain using transmission electron microscopy (TEM) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Smaller PS-NPs (20 nm) showed the highest accumulation in the intestine, followed by the liver, and gills, due to their greater surface area and cellular penetration. In contrast, larger PS-NPs (500 nm) exhibited lower accumulation and clearance rates, especially in the brain, suggesting restricted passage through biological barriers. The intestine consistently had the highest concentrations in both accumulation and depuration, while the brain maintained the lowest across all nanoparticle sizes. During depuration, smaller particles cleared more quickly, whereas larger particles persisted. This study highlights the tissue-specific distribution and retention patterns of PS-NPs in D. rerio, providing insights into nanoparticle behavior in aquatic organisms and the need for long-term size-specific environmental risk assessments.
Keywords: Nano-plastics, D. rerio, bioaccumulation, depuration, tissue-specific distribution, Size-dependent dynamics.
A crescente preocupação com a poluição por microplásticos destaca a urgência em investigar seus efeitos na saúde humana, especialmente o acumulo na placenta e seus esfeitos. Estudos demonstram que as micro e nano partículas plásticas podem translocar-se pelo corpo, alcançando tecidos como a placenta, onde podem se acumular e impactar o desenvolvimento fetal. A exposição materna, como os de poliestireno, tem sido associada a anomalias cerebrais e restrição do crescimento fetal em modelos animais. Embora existam evidências sobre os efeitos agudos da exposição, há uma carência de estudos que explorem os impactos transgeracionais e em níveis de exposição ambientalmente relevantes. A necessidade de desenvolver métodos robustos para caracterizar essa exposição em humanos é imperativa, assim como a realização de investigações a longo prazo para entender quais as reais implicações na saúde das futuras gerações.
The widespread use of plastics has increased environmental pollution by micro- and nanoplastics (MNPs), especially polystyrene micro- and nanoplastics (PS-MNPs). These particles are persistent, bioaccumulative, and linked to endocrine-disrupting toxicity, posing risks to reproductive health. This review examines the effects of PS-MNPs on mammalian reproductive systems, focusing on oxidative stress, inflammation, and hormonal imbalances. A comprehensive search in the Web of Science Core Collection, following PRISMA 2020 guidelines, identified studies on the impact of PS-MNPs on mammalian fertility, including oogenesis, spermatogenesis, and folliculogenesis. An analysis of 194 publications revealed significant reproductive harm, such as reduced ovarian size, depleted follicular reserves, increased apoptosis in somatic cells, and disrupted estrous cycles in females, along with impaired sperm quality and hormonal imbalances in males. These effects were linked to endocrine disruption, oxidative stress, and inflammation, leading to cellular and molecular damage. Further research is urgently needed to understand PS-MNPs toxicity mechanisms, develop interventions, and assess long-term reproductive health impacts across generations, highlighting the need to address these challenges given the growing environmental exposure.
Plastics are versatile materials whose production and use are growing on a global scale. However, inadequate plastic waste management and its degradation result in the release of small particles, namely microplastics (MPs) and nanoplastics (NPs), which have adverse effects in physical, biological, and socioeconomic aspects. United Nations (UN) Sustainable Development Goal (SDG) 2 is related to ending hunger, promoting food security and nutrition, and achieving agricultural sustainability. MPs and NPs may affect the productivity and quality of agricultural products and contaminate foods and beverages from other sources, increasing health risks for human consumers. A systematic bibliographic review was conducted using StArt 3.4 and Excel software to identify gaps and recent advances in selected publications from 2022 and 2023 regarding the impacts of MPs and NPs to UN SDG 2. Then, 310 selected studies that discussed consequences to the agricultural soil, foods, drinking water, and beverages were summarized. The review addressed the recent advances and results regarding sources, occurrence, mobility, and effects of MPs and NPs on soil properties, nutrient cycling, productivity, and quality of agricultural soils. We also explored sources and MPs/NPs contamination of different types of foods, drinking water, and beverages. Hence, we highlighted the presence of plastic particles along the whole food production and consumption, which calls attention to the imperativeness of public policies and changes on plastic waste management cycle. We also reinforce the need for assessing MPs and NPs contamination considering local particularities, such as the climate, most common species, and feeding habits.
Graphical Abstract
Background
Plastic is everywhere. It is used in food packaging, storage containers, electronics, furniture, clothing, and common single-use disposable items. Microplastic and nanoplastic particulates are formed from bulk fragmentation and disintegration of plastic pollution. Plastic particulates have recently been detected in indoor air and remote atmospheric fallout. Due to their small size, microplastic and nanoplastic particulate in the atmosphere can be inhaled and may pose a risk for human health, specifically in susceptible populations. When inhaled, nanosized particles have been shown to translocate across pulmonary cell barriers to secondary organs, including the placenta. However, the potential for maternal-to-fetal translocation of nanosized-plastic particles and the impact of nanoplastic deposition or accumulation on fetal health remain unknown. In this study we investigated whether nanopolystyrene particles can cross the placental barrier and deposit in fetal tissues after maternal pulmonary exposure.
Results
Pregnant Sprague Dawley rats were exposed to 20 nm rhodamine-labeled nanopolystyrene beads (2.64 × 10 ¹⁴ particles) via intratracheal instillation on gestational day (GD) 19. Twenty-four hours later on GD 20, maternal and fetal tissues were evaluated using fluorescent optical imaging. Fetal tissues were fixed for particle visualization with hyperspectral microscopy. Using isolated placental perfusion, a known concentration of nanopolystyrene was injected into the uterine artery. Maternal and fetal effluents were collected for 180 min and assessed for polystyrene particle concentration. Twenty-four hours after maternal exposure, fetal and placental weights were significantly lower (7 and 8%, respectively) compared with controls. Nanopolystyrene particles were detected in the maternal lung, heart, and spleen. Polystyrene nanoparticles were also observed in the placenta, fetal liver, lungs, heart, kidney, and brain suggesting maternal lung-to-fetal tissue nanoparticle translocation in late stage pregnancy.
Conclusion
These studies confirm that maternal pulmonary exposure to nanopolystyrene results in the translocation of plastic particles to placental and fetal tissues and renders the fetoplacental unit vulnerable to adverse effects. These data are vital to the understanding of plastic particulate toxicology and the developmental origins of health and disease.
Background
Women are reported more likely to develop depression and dementia. However, the involved mechanism is poorly understood.
Objective
Here, we clarified the role of estrogen receptor α (ERα) in depression and cognitive deficit in young female rats.
Methods
After being exposed to 7-weeks’ chronic unpredicted mild stress (CUMS), the depression resilient rats (Res rats) and depressed rats (Dep rats) were selected according to their records in sucrose preference test, forced swimming test, and open field test. Their cognition abilities were tested by Morris water maze. Proteomic assay, immunoprecipitation, western blotting, immunohistochemical, and Nissl staining were also used to understand the involved mechanism.
Results
Compared with control rats and Res rats, Dep rats showed cognitive deficits and hippocampal impairments revealed by proteomic data, neuron losses, increased cleaved caspase-3, β-catenin phosphorylation, and glycogen synthase kinase3β (GSK3β) activation. As ERα, but not ERβ, was found declined in hippocampi of Dep rats, 4,4k,4a-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT, an ERα agonist, 1 mg/kg/day), was used to treat Dep rats (Dep + PPT). Twenty days later, the depressive behaviors, cognition deficits, and hippocampal neuron loss were rescued in Dep + PPT rats. Furthermore, Res and Dep + PPT rats had higher levels of β-catenin combined with ERα and lower levels of β-catenin combined with GSK3β than Dep rats in hippocampi.
Conclusion
These results demonstrated hippocampal ERα is an important pro-resilient factor in CUMS-induced depressive behaviors and cognitive deficits. It was also given that the neuroprotection afforded by hippocampal ERα/Wnt interactions have significant implications for cognition and emotion in young females.
Aquatic environments are generally contaminated with nanoplastic material. As a result, molecular mechanisms for sensitive species like Daphnia are needed, given that mechanistic nanoplastic toxicity is largely unknown. Here, global transcriptome sequencing (RNA-Seq) was performed on D. pulex neonates to quantitatively measure the expression level of transcripts. A total of 208 differentially expressed genes (DEGs) were detected in response to nanoplastic exposure for 96 h, with 107 being up-regulated and 101 down-regulated. The gene functions and pathways for oxidative stress, immune defense, and glycometabolism were identified. In this study, D. pulex neonates provide some molecular insights into nanoplastic toxicity. However, more studies on DEGs are needed to better understand the underlying mechanisms that result as a response to nanoplastic toxicity in aquatic organisms.
Microplastics are particles smaller than five millimetres obtained from the degradation of plastic objects abandoned in the environment. Microplastics can move from the environment to living organisms and, in fact, they have been found in fishes and mammals.
Six human placentas, prospectively collected from consenting women with uneventful pregnancies, were analyzed by Raman Microspectroscopy to evaluate the presence of microparticles. Detected microparticles were characterized in terms of morphology and chemical composition.
12 microparticles, ranging from 5 to 10 γm in size, were found in 4 out of 6 placentas: 5 in the foetal side, 4 in the maternal side and 3 in the chorioamniotic membranes. All the analyzed microparticles were pigmented: three of them were identified as stained polypropylene, while for the other nine it was possible to identify only the pigments, which are all used for man-made coatings, paints and dyes.
Here we show, for the first time, the presence of microparticles and microplastics in human placenta. This sheds new light on the impact of plastic on human health. Microparticles and microplastics in the placenta, together with the endocrine disruptors transported by them, could have long-term effects on human health.
Although the fates of microplastics (0.1–5 mm in size) and nanoplastics (<100 nm) in marine environments are being increasingly well studied1,2, little is known about the behaviour of nanoplastics in terrestrial environments3–6, especially agricultural soils⁷. Previous studies have evaluated the consequences of nanoplastic accumulation in aquatic plants, but there is no direct evidence for the internalization of nanoplastics in terrestrial plants. Here, we show that both positively and negatively charged nanoplastics can accumulate in Arabidopsis thaliana. The aggregation promoted by the growth medium and root exudates limited the uptake of amino-modified polystyrene nanoplastics with positive surface charges. Thus, positively charged nanoplastics accumulated at relatively low levels in the root tips, but these nanoplastics induced a higher accumulation of reactive oxygen species and inhibited plant growth and seedling development more strongly than negatively charged sulfonic-acid-modified nanoplastics. By contrast, the negatively charged nanoplastics were observed frequently in the apoplast and xylem. Our findings provide direct evidence that nanoplastics can accumulate in plants, depending on their surface charge. Plant accumulation of nanoplastics can have both direct ecological effects and implications for agricultural sustainability and food safety.
Aquatic ecosystems are globally contaminated with microplastics (MP). However, comparative data on MP levels in freshwater systems is still scarce. Therefore, the aim of this study is to quantify MP abundance in water and sediment of the German river Elbe using visual, spectroscopic (Fourier-transform infrared spectroscopy) and thermo analytical (pyrolysis gas chromatography mass spectrometry) methods. Samples from eleven German sites along the German part of the Elbe were collected, both in water and sediment phase, in order to better understand MP sinks and transport mechanisms. MP concentrations differed between the water and sediment phase. Sediment concentrations (mean: 3,350,000 particles m⁻³, 125–5000 μm MP) were in average 600,000-fold higher than water concentrations (mean: 5.57 particles m⁻³, 150–5000 μm MP). The abundance varied between the sampling sites: In sediments, the abundance decreased in the course of the river while in water samples no such clear trend was observed. This may be explained by a barrage retaining sediments and tidal influence in the upstream parts of the river. Particle shape differed sitespecifically with one site having exceptionally high quantities of spheres, most probably due to industrial emissions of PS-DVB resin beads. Suspended MP consisted predominantly of polyethylene and polypropylene whereas sediments contained a higher diversity of polymer types. Determined MP concentrations correspond well to previous results from other European rivers. In a global context, MP levels in the Elbe relate to the lower (water) to middle section (sediment) of the global range of MP concentrations determined for rivers worldwide. This highlights that elevated MP levels are not only found in single countries or continents, but that MP pollution is an issue of global concern.
Drug-protein binding plays a key role in determining the pharmacokinetics of a drug. The distribution and protein binding ability of a drug changes over a lifetime, and are important considerations during pregnancy and lactation. Although proteins are a significant fraction in plasma composition, they also exist beyond the bloodstream and bind with drugs in the skin, tissues or organs. Protein binding influences the bioavailability and distribution of active compounds, and is a limiting factor in the passage of drugs across biological membranes and barriers: drugs are often unable to cross membranes mainly due to the high molecular mass of the drug-protein complex, thus resulting in the accumulation of the active compounds and a significant reduction of their pharmacological activity. This review describes the consequences of drug-protein binding on drug transport across physiological barriers, whose role is to allow the passage of essential substances—such as nutrients or oxygen, but not of xenobiotics. The placental barrier regulates passage of xenobiotics into a fetus and protects the unborn organism. The blood–brain barrier is the most important barrier in the entire organism and the skin separates the human body from the environment.
Microplastics have recently been detected in the atmosphere of urban, suburban, and even remote areas far away from source regions of microplastics, suggesting the potential long-distance atmospheric transport for microplastics. There still exist questions regarding the occurrence, fate, transport, and effect of atmospheric microplastics. These questions arise due to limited physical analysis and understanding of atmospheric microplastic pollution in conjunction with a lack of standardized sampling and identification methods. This paper reviews the current status of knowledge on atmospheric microplastics, the methods for sample collection, analysis and detection. We review and compare the methods used in the previous studies and provide recommendations for atmospheric microplastic sampling and measurement. Furthermore, we summarize the findings related to atmospheric microplastic characteristics, including abundance, size, shapes, colours, and polymer types. Microplastics occur in the atmosphere from urban to remote areas, with an abundance/deposition spanning 1–3 orders of magnitude across different sites. Fibres and fragments are the most frequently reported shapes and the types of plastic which generally aligns with world plastic demand. We conclude that atmospheric microplastics require further research and greater understanding to identify its global distributions and potential exposure to human health through further field sampling and implementation of standardized analytical protocols.
Research on microplastics in soils is still uncommon and the existing publications are often incomparable due to the use of different sampling, processing and analytical methods. Given the complex nature of soils, a suitable and efficient method for standardised microplastic analysis in the soil matrix has yet to be found. This paper proposes a critical review on the different published methods for sampling, extraction, purification and identification/quantification of microplastics in complex environmental matrices, with the main focus on their applicability for soil samples. While large microplastic particles can be manually sorted out and verified with chemical analysis, sample preparation for smaller microplastic analysis is usually more difficult. Of the analytical approaches proposed in literature, some are established, while others are a proof of principle and have not yet been applied to environmental samples. For the sake of development all approaches are discussed and assessed for their potential applicability for soil samples. So far, none of the published methods seems ideally suitable for the analysis of smaller microplastics in soil samples, but slight modifications and combinations of methods may prove promising and need to be explored.
Recently, research on the biological effects of nanoplastics has grown exponentially. However, studies on the effects of nanoplastics on freshwater organisms and the mechanisms of the biological effects of nanoplastics are limited. In this study, the content of reactive oxygen species (ROS), gene and protein expression in the MAPK-HIF-1/NFkB pathway, and antioxidant gene expressions and enzyme activities were measured in Daphnia pulex exposed to polystyrene nanoplastic. In addition, the full-length extracellular signal-regulated kinases (ERK) gene, which plays an important role in the MAPK pathway, was cloned in D. pulex, and the amino acid sequence, function domain, and phylogenetic tree were analyzed. The results show that nanoplastic caused the overproduction of ROS along with other dose-dependent effects. Low nanoplastic concentrations (0.1 and/or 0.5 mg/L) significantly increased the expressions of genes of the MAPK pathway (ERK; p38 mitogen-activated protein kinases, p38; c-Jun amino-terminal kinases, JNK; and protein kinase B, AKT), HIF-1 pathway ( prolyl hydroxylasedomain, PHD; vascular endothelial growth factor, VEGF; glucose transporter, GLUT; pyruvate kinase M, PKM; hypoxia-inducible factor 1, HIF1), and CuZn superoxide dismutase (SOD) along with the activity of glutathione-S-transferase. As the nanoplastic concentration increased, these indicators were significantly suppressed. The protein expression ratio of ERK, JNK, AKT, HIF1α, and NFkBp65 (nuclear transcription factor-kB p65) as well as the phosphorylation of ERK and NFkBp65 were increased in a dose-dependent manner. The activities of other antioxidant enzymes (catalase, total SOD, and CuZn SOD) were significantly decreased upon exposure to nanoplastic. Combined with our previous work, these results suggest that polystyrene nanoplastic causes the overproduction of ROS and activates the downstream pathway, resulting in inhibited growth, development, and reproduction. The present study fosters a better understanding of the biological effects of nanoplastics on zooplankton.
The growing application of gene expression profiling demands powerful yet user-friendly bioinformatics tools to support systems-level data understanding. NetworkAnalyst was first released in 2014 to address the key need for interpreting gene expression data within the context of protein-protein interaction (PPI) networks. It was soon updated for gene expression meta-analysis with improved workflow and performance. Over the years, NetworkAnalyst has been continuously updated based on community feedback and technology progresses. Users can now perform gene expression profiling for 17 different species. In addition to generic PPI networks, users can now create cell-type or tissue specific PPI networks, gene regulatory networks, gene co-expression networks as well as networks for toxicogenomics and pharmacogenomics studies. The resulting networks can be customized and explored in 2D, 3D as well as Virtual Reality (VR) space. For meta-analysis, users can now visually compare multiple gene lists through interactive heatmaps, enrichment networks, Venn diagrams or chord diagrams. In addition, users have the option to create their own data analysis projects, which can be saved and resumed at a later time. These new features are released together as NetworkAnalyst 3.0, freely available at https://www.networkanalyst.ca.
A critical component in the interpretation of systems-level studies is the inference of enriched biological pathways and protein complexes contained within OMICs datasets. Successful analysis requires the integration of a broad set of current biological databases and the application of a robust analytical pipeline to produce readily interpretable results. Metascape is a web-based portal designed to provide a comprehensive gene list annotation and analysis resource for experimental biologists. In terms of design features, Metascape combines functional enrichment, interactome analysis, gene annotation, and membership search to leverage over 40 independent knowledgebases within one integrated portal. Additionally, it facilitates comparative analyses of datasets across multiple independent and orthogonal experiments. Metascape provides a significantly simplified user experience through a one-click Express Analysis interface to generate interpretable outputs. Taken together, Metascape is an effective and efficient tool for experimental biologists to comprehensively analyze and interpret OMICs-based studies in the big data era.
Neonatal encephalopathy due to hypoxia ischemia (HI) leads to severe, life-long morbidities in thousands of neonates born in the US and worldwide each year. Varying capacities of long-term episodic memory, verbal working memory and learning can present without cerebral palsy and have been associated with the severity of neonatal encephalopathy sustained at birth. Among children who sustain a moderate degree of HI at birth, girls have larger hippocampal volumes compared to boys. Clinical studies indicate that female neonatal brains are more resistant to the effects of neonatal HI, resulting in better long-term cognitive outcomes as compared to males with comparable brain injury. Our most recent mechanistic studies have addressed the origins and cellular basis of sex differences in hippocampal neuroprotection following neonatal HI-related brain injury, and implicate estrogen receptor α(ERα) in the neurotrophin receptor-mediated hippocampal neuroprotection in female mice. This review summarizes the recent findings on ERα dependent, neurotrophin-mediated hippocampal neuroprotection, and weighs the evidence that this mechanism plays an important role in preserving long-term memory and learning following HI in females.
Emerging evidence now indicates that mitochondria are central regulators of neural stem cell (NSC) fate decisions and are crucial for both neurodevelopment and adult neurogenesis, which in turn contribute to cognitive processes in the mature brain. Inherited mutations and accumulated damage to mitochondria over the course of ageing serve as key factors underlying cognitive defects in neurodevelopmental disorders and neurodegenerative diseases, respectively. In this Review, we explore the recent findings that implicate mitochondria as crucial regulators of NSC function and cognition. In this respect, mitochondria may serve as targets for stem-cell-based therapies and interventions for cognitive defects.
Little is known about how 17β-estradiol (E2) mediates memory formation in males. In ovariectomized (OVX) mice, bilateral dorsal hippocampal (DH) infusion of E2 enhances memory consolidation in object recognition (OR) and object placement (OP) tasks in a manner dependent on activation of extracellular signal-regulated kinase (ERK) and Akt signaling. Here, bilateral DH E2 infusion enhanced memory consolidation in both tasks among OVX female, gonadally-intact male, and castrated male mice, suggesting comparable facilitation of memory consolidation in both sexes, independent of testicular hormones in males. Contrary to previous reports in OVX mice, E2 did not increase DH ERK or Akt phosphorylation in males, nor did the ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis (o-aminophenylmercapto) butadiene] prevent E2 from enhancing memory consolidation among intact and castrated males. These data suggest that ERK activation is not necessary for E2 to enhance memory consolidation in males, and compared with previous reports in females, reveal novel sex differences in the cell-signaling pathways through which E2 facilitates memory consolidation. To explore the mechanisms underlying E2-induced memory enhancements in males, phosphorylation of the transcription factor cAMP response element binding protein (CREB) in the DH was assessed. E2 increased phospho-CREB levels in both sexes, yet U0126 did not block these increases in castrated or intact males, indicating that E2 regulates CREB phosphorylation in males via an ERK-independent mechanism. Collectively, these findings suggest that the beneficial effects of hippocampal E2 on memory consolidation in males and females are mediated by different molecular mechanisms, which has important implications for the development of treatments to reduce memory dysfunction in men and women.
Piperlongumine (PL), a biologically active compound from the Piper species, has been shown to exert various pharmacological effects in a number of conditions, including tumours, diabetes, pain, psychiatric disorders and neurodegenerative disease. In this study, we evaluated the therapeutic effects of PL on hippocampal function and cognition decline in aged mice. PL (50 mg/kg/day) was intragastrically administrated to 23‑month‑old female C57BL/6J mice for 8 weeks. Novel object recognition and nest building behaviour tests were used to assess cognitive and social functions. Additionally, immunohistochemistry and western blot analysis were performed to examine the effects of PL on the hippocampus. We found that the oral administration of PL significantly improved novel object recognition and nest building behaviour in aged mice. Although neither the percentage area occupied by astrocytes and microglia nor the level of 4‑hydroxynonenal protein, a specific marker of lipid peroxidation, were altered by PL treatment, the phosphorylation levels of N‑methyl‑D‑aspartate receptor subtype 2B (NR2B), calmodulin‑dependent protein kinase II alpha (CaMKIIα) and extracellular signal‑regulated kinase 1/2 (ERK1/2) were markedly increased in the hippocampus of aged mice following the administration of PL. We also found that PL treatment resulted in a CA3‑specific increase in the phosphorylation level of cyclic AMP response element binding protein, which is recognized as a potent marker of neuronal plasticity, learning and memory. Moreover, the number of doublecortin‑positive cells, a specific marker of neurogenesis, was significantly increased following PL treatment in the dentate gyrus of the hippocampus. On the whole, these data demonstrate that PL treatment may be a potential novel approach in the treatment of age‑related cognitive impairment and hippocampal changes.
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease (PD). LRRK2 contains a functional kinase domain and G2019S, the most prevalent LRRK2 pathogenic mutation, increases its kinase activity. LRRK2 regulates mitochondria morphology and autophagy in neurons. LPS treatment increases LRRK2 protein level and mitochondrial fission in microglia, and down-regulation of LRRK2 expression or inhibition of its kinase activity attenuates microglia activation. Here, we evaluated the direct role of LRRK2 G2019S in mitochondrial dynamics in microglia. Initial observation of microglia in G2019S transgenic mice revealed a decrease in mitochondrial area and shortage of microglial processes compared with their littermates. Next, we elucidated the molecular mechanisms of these phenotypes. Treatment of BV2 cells and primary microglia with LPS enhanced mitochondrial fission and increased Drp1, a mitochondrial fission marker, as previously reported. Importantly, both phenotypes were rescued by treatment with GSK2578215A, a LRRK2 kinase inhibitor. Finally, the protein levels of CD68, an active microglia marker, Drp1 and TNF-α were significantly higher in brain lysates of G2019S transgenic mice compared with the levels in their littermates. Taken together, our data suggest that LRRK2 could promote microglial mitochondrial alteration via Drp1 in a kinase-dependent manner, resulting in stimulation of pro-inflammatory responses. This mechanism in microglia might be a potential target to develop PD therapy since neuroinflammation by active microglia is a major symptom of PD.
Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the “blood‐brain barrier”. These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood‐brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting. This article is protected by copyright. All rights reserved
Recently, we have reported that animals with telomerase reverse transcriptase (TERT) overexpression exhibit reduced social interaction, decreased preference for novel social interaction and poor nest-building behaviors-symptoms that mirror those observed in human autism spectrum disorders (ASD). Overexpression of TERT also alters the excitatory/inhibitory (E/I) ratio in the medial prefrontal cortex. However, the effects of TERT overexpression on hippocampal-dependent learning and synaptic efficacy have not been investigated. In the present study, we employed electrophysiological approaches in combination with behavioral analysis to examine hippocampal function of TERT transgenic (TERT-tg) mice and FVB controls. We found that TERT overexpression results in enhanced hippocampal excitation with no changes in inhibition and significantly impairs long-term synaptic plasticity. Interestingly, the expression levels of phosphorylated CREB and phosphorylated CaMKIIα were significantly decreased while the expression level of CaMKIIα was slightly increased in the hippocampus of TERT-overexpressing mice. Our observations highlight the importance of TERT in normal synaptic function and behavior and provide additional information on a novel animal model of ASD associated with TERT overexpression.
Polymer-based multilayer packaging materials are commonly used in order to combine the respective performance of different polymers. By this approach, the tailored functionality of packaging concepts is created to sufficiently protect sensitive food products and thus obtain extended shelf life. However, because of their poor recyclability, most multilayers are usually incinerated or landfilled, counteracting the efforts towards a circular economy and crude oil independency. This review depicts the current state of the European multilayer packaging market and sketches the current end-of-life situation of postconsumer multilayer packaging waste in Germany. In the main section, a general overview of the state of research about material recycling of different multilayer packaging systems is provided. It is divided into two subsections, whereby one describes methods to achieve a separation of the different components, either by delamination or the selective dissolution–reprecipitation technique, and the other describes methods to achieve recycling by compatibilization of nonmiscible polymer types. While compatibilization methods and the technique of dissolution–reprecipitation are already extensively studied, the delamination of packaging has not been investigated systematically. All the presented options are able to recycle multilayer packaging, but also have drawbacks like a limited scope or a high expenditure of energy.
Abnormal potentiation in the lateral habenula (LHb) has been suggested to mediate depression-like behaviors. However, the underlying mechanisms of the synaptic efficacy regulation of LHb synapses and the potential for their modulation are only poorly understood. Here, we report that long-term synaptic depression (LTD) occurs in the LHb upon both low-frequency stimulation (LFS) and moderate-frequency stimulation (MFS). LFS-induced LTD (LFS-LTD) is accompanied by a reduction in presynaptic release probability, which is endocannabinoid (eCB) signaling dependent. Surprisingly, exposure to an acute stressor completely masks the induction of LFS-LTD in the LHb while leaving the MFS-induced LTD intact. Pharmacological activation of cannabinoid receptor 1 (CB1R) or blockade of αCaMKII successfully restored LTD in the LHb in an animal model of depression. Thus, our findings reveal a form of synaptic strength regulation and a stress-induced shift of synaptic plasticity in the LHb.
Mitochondrial dysfunction is a common feature of many genetic disorders that target the brain and cognition. However, the exact role these organelles play in the etiology of such disorders is not understood. Here we show that mitochondrial dysfunction impairs brain development, depletes the adult neural stem cell (NSC) pool and impacts embryonic and adult neurogenesis. Using deletion of the mitochondrial oxidoreductase AIF as a genetic model of mitochondrial and neurodegenerative diseases revealed the importance of mitochondria in multiple steps of the neurogenic process. Developmentally, impaired mitochondrial function causes defects in NSC self-renewal, neural progenitor cell (NPC) proliferation and cell cycle exit, as well as neuronal differentiation. Sustained mitochondrial dysfunction into adulthood leads to NSC depletion, loss of adult neurogenesis and manifests as a decline in brain function and cognitive impairment. These data demonstrate that mitochondrial dysfunction, as observed in genetic mitochondrial and neurodegenerative diseases, underlies the decline of brain function and cognition due to impaired stem cell maintenance and neurogenesis.
Microplastics (MPs) are a significant environmental health issue and increasingly greater source of concern. MPs have been detected in oceans, rivers, sediments, sewages, soil and even table salts. MPs exposure on marine organisms and humans has been documented, but information about the toxicity of MPs in mammal is limited. Here we used fluorescent and pristine polystyrene microplastics (PS-MPs) particles with two diameters (5 μm and 20 μm) to investigate the tissue distribution, accumulation, and tissue-specific health risk of MPs in mice. Results indicated that MPs accumulated in liver, kidney and gut, with a tissue-accumulation kinetics and distribution pattern that was strongly depended on the MPs particle size. In addition, analyses of multiple biochemical biomarkers and metabolomic profiles suggested that MPs exposure induced disturbance of energy and lipid metabolism as well as oxidative stress. Interestingly, blood biomarkers of neurotoxicity were also altered. Our results uncovered the distribution and accumulation of MPs across mice tissues and revealed significant alteration in several biomarkers that indicate potential toxicity from MPs exposure. Collectively, our data provided new evidence for the adverse consequences of MPs.
Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and anti-mycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid β (Aβ) deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aβ and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.
Children in America today are at an unacceptably high risk of developing neurodevelopmental disorders that affect the brain and nervous system including autism, attention deficit hyperactivity disorder, intellectual disabilities, and other learning and behavioral disabilities. These are complex disorders with multiple causes—genetic, social, and environmental. The contribution of toxic chemicals to these disorders can be prevented. Approach: Leading scientific and medical experts, along with children’s health advocates, came together in 2015 under the auspices of Project TENDR: Targeting Environmental Neuro-Developmental Risks to issue a call to action to reduce widespread exposures to chemicals that interfere with fetal and children’s brain development. Based on the available scientific evidence, the TENDR authors have identified prime examples of toxic chemicals and pollutants that increase children’s risks for neurodevelopmental disorders. These include chemicals that are used extensively in consumer products and that have become widespread in the environment. Some are chemicals to which children and pregnant women are regularly exposed, and they are detected in the bodies of virtually all Americans in national surveys conducted by the U.S. Centers for Disease Control and Prevention. The vast majority of chemicals in industrial and consumer products undergo almost no testing for developmental neurotoxicity or other health effects. Conclusion: Based on these findings, we assert that the current system in the United States for evaluating scientific evidence and making health-based decisions about environmental chemicals is fundamentally broken. To help reduce the unacceptably high prevalence of neurodevelopmental disorders in our children, we must eliminate or significantly reduce exposures to chemicals that contribute to these conditions. We must adopt a new framework for assessing chemicals that have the potential to disrupt brain development and prevent the use of those that may pose a risk. This consensus statement lays the foundation for developing recommendations to monitor, assess, and reduce exposures to neurotoxic chemicals. These measures are urgently needed if we are to protect healthy brain development so that current and future generations can reach their fullest potential.
Rapid modulation of hippocampal synaptic plasticity through synaptic estrogen receptors is an essential topic. We analyzed estradiol-induced modulation of CA1 dendritic spines using adult male ERαKO and ERβKO mice. A 2h treatment of estradiol particularly increased the density of middle-head spines (diameter 0.3-0.4µm) in wild type mouse hippocampal slices. The enhancement of spinogenesis was completely suppressed by MAP kinase inhibitor. Estradiol-induced increase in middle-head spines was observed in ERβKO mice (which express ERα), but not in ERαKO, indicating that ERα is necessary for the spinogenesis. Direct observation of the dynamic estradiol-induced enhancing effect on rapid spinogenesis was performed using time-lapse imaging of spines in hippocampal live slices from yellow fluorescent protein expressed mice. Both appearance and disappearance of spines occurred, and the number of newly appeared spines was significantly greater than that of disappeared spines, resulting in the net increase of the spine density within 2h. As another type of synaptic modulation, we observed that estradiol rapidly enhanced N-methyl-D-aspartate (NMDA)-induced long-term depression (LTD) in CA1 of the wild type mouse hippocampus. In contrast, estradiol did not enhance NMDA-LTD in ERαKO mice, indicating the involvement of ERα in the estrogen signaling. This article is part of a Special Issue entitled SI: Brain and Memory.
Copyright © 2014. Published by Elsevier B.V.
TopHat is a popular spliced aligner for RNA-seq experiments. Here, we describe TopHat2, which incorporates many significant enhancements to TopHat. TopHat2 can align reads of various lengths produced by the latest sequencing technologies, while allowing for variable-length indels with respect to the reference genome. In addition to de novo spliced alignment, TopHat2 can align reads across fusion breaks, which occur after genomic translocations. TopHat2 combines the ability to discover novel splice sites with direct mapping to known transcripts, producing sensitive and accurate alignments, even for highly repetitive genomes or in the presence of pseudogenes. TopHat2 is available at http://ccb.jhu.edu/software/tophat.
The toxic mechanisms of functionalized polystyrene nanoplastics (NPs) in bivalves, especially regarding energy homeostasis and immunity in benthic marine ecosystem, are poorly understood. Therefore, in this study, the toxicity effects of two amino-modified and carboxylated polystyrene NPs (PS-NH2and PS-COOH) on clams (Meretrix meretrix) at individual, organic, cellular, and gene levels were investigated at environmentally relevant NP concentrations of 0.02-2 mg L⁻¹. The exposure of both NPs showed non-lethal effect but inhibited the clam growth. Little difference in the toxic effect was observed between the two NPs, mainly due to their similar bioaccessibility. The inhibition of clam growth was mainly driven by the energy homeostasis imbalanceviathe atrophic inflammation of digestive glands induced by the bioaccumulation of NPs. The immunomodulation dysfunction, manifested as decreased phagocytosis resulting from the lysosomal membrane destabilization, was also responsible for the inhibited growth. Furthermore, the mechanisms of genotoxicity were identified to be energy homeostasis imbalance triggered by pancreatic secretion, tricarboxylic acid cycle (TCA) cycle, and peroxisome proliferator activated-receptor α (PPARα) signaling pathway, and the immunomodulation dysregulation dominated by the constrained toll-like receptors (TLR) and nuclear factor-kappa B (NF-κB) signaling pathway, phagosome and lysosome pathway. This work has expanded the current understanding of the toxic mechanisms of functionalized NPs in bivalves, highlighting the potential risks of the NPs in the stability and function of marine benthic ecosystems, even food security.
Microplastics which are gradually and randomly decompose into small fragment by exposure of physical and biological external stress are emerging as a significant threat to the all the environments. Here, we have demonstrated the in vitro toxicity of microplastics of two different shapes. To minimize the chemical effect, polyethylene (PE), was used. PE microplastics with two different shapes were prepared, high-density PE microbeads and irregularly ground low-density PE from bulk pellets. It is hypothesized that morphological characteristics and concentration of PE microplastics could affect cellular viability, immunity, and lysis. To quantify the randomness of the microplastic shape, the edge patterns of the generated PE microplastics were converted into numerical values and analyzed using a statistical method. A 10-fold difference in curvature value was observed between microbeads and ground microfragments. To correlate shape differences to toxicology, cells were exposed to PE microplastics on the demand of toxicology studies. We found that the higher concentration and rough structure were associated with the toxicity of plastics toward cells, pro-inflammatory cytokine release, and hemolysis, even though PE is buoyant onto medium. The PE microbeads did not exhibit severe cytotoxicity at any of the tested concentrations, but induced immune and hemolysis responses at high concentrations. When comparing the toxicity of different shapes of PE microplastics, we confirmed by statistical analysis that irregular-shape plastics with sharp edges and higher curvature differences may adversely affect cells, further having possibility to human toxicity in real environment.
Microplastics (MPs) have become hazardous materials, which have aroused widespread concern about their potential toxicity. However, the effects of MPs on reproductive systems in mammals are still ambiguous. In this study, the toxic effects of polystyrene MPs (PS-MPs) in male reproduction of mice were investigated. The results indicated that after exposure for 24 h, 4 μm and 10 μm PS-MPs accumulated in the testis of mice. Meanwhile, 0.5 μm, 4 μm, and 10 μm PS-MPs could enter into three kinds of testicular cells in vitro. In addition, sperm quality and testosterone level of mice were declined after exposure to 0.5 μm, 4 μm, and 10 μm PS-MPs for 28 days. H&E staining showed that spermatogenic cells abscissed and arranged disorderly, and multinucleated gonocytes occurred in the seminiferous tubule. Moreover, PS-MPs induced testicular inflammation and the disruption of blood-testis barrier. In summary, this study demonstrated that PS-MPs induced male reproductive dysfunctions in mice, which provided new insights into the toxicity of MPs in mammals.
With the increase in plastic production, a variety of toxicological studies on microplastics have been conducted as microplastics can be accumulated in the human body and cause unknown disease. However, previous studies have mainly assessed the toxicity of sphere-type microbeads, which may differ from randomly-shaped microplastics in a real environment. Here, we conducted in vitro toxicology analysis for randomly-shaped microplastics based on the hypotheses that (1) physical cytotoxicity is affected by nano-/micro-size roughness in polystyrene (PS) microfragments and (2) chemical toxicity is caused by chemical reagents from microplastics. We confirmed that the PS microfragments increased the acute inflammation of immune cells 20 times than control, the production of reactive oxygen species, and cell death of fibroblasts and cancer cells by releasing chemical reagents. In addition, when the PS microfragments were in direct contact with fibroblasts and red blood cells, the physical stress caused by them resulted in lactose dehydrogenase and hemoglobin release, respectively, due to cell membrane damage and hemolysis. This phenomenon was amplified when the concentration and roughness of the microfragments increased. Moreover, we quantitatively analyzed roughness differences between microplastics, which revealed a strong relationship between the physical damage of cells and the roughness of microplastics.
In this study, the hypothesis that polyethylene microplastics (MPs) can accumulate in animals, reach the upper trophic level and trigger behavioral changes was tested. Physalaemus cuvieri tadpoles were exposed to MPs (for 7 days) and fed on tambatinga fish for the same period. Subsequently, these fish were given as food to Swiss mice. The MP amount in animals’ liver was quantified and results have evidenced its accumulation at all assessed trophic levels [tadpole: 18,201.9 particles/g; fish: 1.26 particles/g; mice receiving tambatingas who had fed on tadpoles exposed to MPs: 57.07 particles/g and mice receiving water added with MPs: 89.12 particles/g). Such accumulation in the last group was associated with shorter traveled distance, slower locomotion speed and higher anxiety index in the open field test. Mice receiving tambatingas who had fed on tadpoles exposed to MPs were confronted to a potential predator and showed responses similar to those of animals who had ingested water added with MPs (lack of defensive social aggregation and reduced risk assessment behavior). Thus, results have preliminarily confirmed the initial hypothesis about how MPs in water can reach terrestrial trophic levels and have negative impact on the survival of these animals.
Microplastics as new emerging pollutants in aquatic environments have received much attention in recent years. However, up to now, microplastic contamination in tap water has only been investigated by few studies. Therefore, this study investigated the presence of microplastics in tap water. 38 tap water samples were taken at different cities of China. The amount of microplastics in tap water varied from 440 ± 275 particles L⁻¹. Particles smaller than 50 μm significantly predominated in most of the tap water samples. Further, according to the shape of these particles, fragments, fibers and spheres were found in tap water samples, while fragments were the most abundant morphotype in most samples. Despite these particles were identified as 14 different materials by micro-Raman spectroscopy, the majority of the microplastics comprised of polyethylene and polypropylene. Based on this investigation, drinking water treatment plants seemingly have to face the problem of microplastic pollution in tap water due to their potential eco-toxicological effects on humans.
Microplastics are ubiquitous across ecosystems, yet the exposure risk to humans is unresolved. Focusing on the American diet, we evaluated the number of microplastic particles in commonly consumed foods in relation to their recommended daily intake. The potential for microplastic inhalation and how the source of drinking water may affect microplastic consumption were also explored. Our analysis used 402 data points from 26 studies, which represents over 3600 processed samples. Evaluating approximately 15% of Americans' caloric intake, we estimate that annual microplastics consumption ranges from 39000 to 52000 particles depending on age and sex. These estimates increase to 74000 and 121000 when inhalation is considered. Additionally, individuals who meet their recommended water intake through only bottled sources may be ingesting an additional 90000 microplastics annually, compared to 4000 microplastics for those who consume only tap water. These estimates are subject to large amounts of variation; however, given methodological and data limitations, these values are likely underestimates.
Spastin is a microtubule-severing enzyme encoded by SPAST, which is broadly expressed in various cell types originated from multiple organs. Even though SPAST is well known as a regulator of the axon growth and arborization in neurons and a genetic factor of hereditary spastic paraplegia, it also takes part in a wide range of other cellular functions including the regulation of cell division and proliferation. In this study, we investigated a novel biological role of spastin in developing brain using Spast deficient mouse embryonic neural stem cells (NSCs) and perinatal mouse brain. We found that the expression of spastin begins at early embryonic stages in mouse brain. Using Spast shRNA treated NSCs and mouse brain, we showed that Spast deficiency leads to decrease of NSC proliferation and neuronal lineage differentiation. Finally, we found that spastin controls NSC proliferation by regulating microtubule dynamics in primary cilia. Collectively, these data demonstrate that spastin controls brain development by the regulation of NSC functions at early developmental stages.
Despite growing plastic discharge into the environment, researchers have struggled to detect expected increases of marine plastic debris in sea surfaces, sparking discussions about “missing plastics” and final sinks, which are hypothesized to be coastal and deep-sea sediments. While it holds true that the highest concentrations of plastic particles are found in these locations (10 ³ -10 ⁴ particles m ⁻³ in sediments vs. 0.1–1 particles m ⁻³ in the water column), our meta-analysis also highlights that in open oceans, microplastic polymer types segregated in the water column according to their density. Lower density polymers, such as polypropylene and polyethylene, dominated sea surface samples (25% and 42%, respectively) but decreased in abundance through the water column (3% and 2% in the deep-sea, respectively), whereas only denser polymers (i.e. polyesters and acrylics) were enriched with depth (5% in surface seawater vs. 77% in deep-sea locations). Our meta-analysis demonstrates that some of the most abundant and recalcitrant manufactured plastics are more persistent in the sea surface than previously anticipated and that further research is required to determine the ultimate fate of these polymers as current knowledge does not support the deep sea as the final sink for all polymer types.
On account of environmental concerns, the fate and adverse effects of plastics have attracted considerable interest in the last years. Recent studies have indicated the potential for fragmentation of plastic materials into nanoparticles, i.e., “nanoplastics” and their possible accumulation in the environment. Nanoparticles can show markedly different chemical and physical properties than their bulk material form. Therefore, possible risks and hazards to the environment need to be considered and addressed. However, the fate and effect of nanoplastics in the (aquatic) environment has so far been little explored. In this review, we aim to provide an overview of the literature on this emerging topic, with an emphasis on the reported impacts of nanoplastics on human health, including the challenges involved in detecting plastics in a biological environment. We first discuss the possible sources of nanoplastics, their fates and effects in the environment and then describe the possible entry routes of these particles into the human body, as well as their uptake mechanisms at the cellular level. Since the potential risks of environmental nanoplastics to humans have not yet been extensively studied, we focus on studies demonstrating cell responses induced by polystyrene nanoparticles. In particular, the influence of particle size and surface chemistry are discussed, in order to understand the possible risks of nanoplastics for humans and provide recommendations for future studies.
As nano- and micro-sized plastics accumulate in the environment and the food chain of animals, including humans, it is imperative to assess the effects of nanoplastics in living organisms in a systematic manner, especially because of their ability to adsorb potential toxicants such as pollutants, heavy metals, and organic macromolecules that coexist in the environment. Using the zebrafish embryo as an animal model, we investigated the bioaccumulation and in vivo toxicity of polystyrene (PS) nanoplastics individually or in combination with the Au ion. We showed that smaller PS nanoplastics readily penetrated the chorion and developing embryos and accumulated throughout the whole body, mostly in lipid-rich regions such as in yolk lipids. We also showed that PS nanoplastics induced only marginal effects on the survival, hatching rate, developmental abnormalities, and cell death of zebrafish embryos but that these effects were synergistically exacerbated by the Au ion in a dose- and size-dependent manner. Such exacerbation of toxicity was well correlated with the production of reactive oxygen species and the pro-inflammatory responses synergized by the presence of PS, supporting the combined toxicity of PS and Au ions. The synergistic effect of PS on toxicity appeared to relate to mitochondrial damage as determined by ultrastructural analysis. Taken together, the effects of PS nanoplastics were marginal but could be a trigger for exacerbating the toxicity induced by other toxicants such as metal ions.
Plastic pollution is a critical environmental concern and comprises the majority of anthropogenic debris in the ocean, including macro, micro, and likely nanoscale (less than 100nm in at least one dimension) plastic particles. While the toxicity of macroplastics and microplastics is relatively well studied, the toxicity of nanoplastics is largely uncharacterized. Here, fluorescent polystyrene nanoparticles (PS NPs) were used to investigate the potential toxicity of nanoplastics in developing zebrafish (Danio rerio), as well as to characterize the uptake and distribution of the particles within embryos and larvae. Zebrafish embryos at 6h post-fertilization (hpf) were exposed to PS NPs (0.1, 1, or 10ppm) until 120 hpf. Our results demonstrate that PS NPs accumulated in the yolk sac as early as 24 hpf and migrated to the gastrointestinal tract, gallbladder, liver, pancreas, heart, and brain throughout development (48-120 hpf). Accumulation of PS NPs decreased during the depuration phase (120-168 hpf) in all organs, but at a slower rate in the pancreas and gastrointestinal tract. Notably, exposure to PS NPs did not induce significant mortality, deformities, or changes to mitochondrial bioenergetics, but did decrease the heart rate. Lastly, exposure to PS NPs altered larval behavior as evidenced by swimming hypoactivity in exposed larvae. Taken together, these data suggest that at least some nanoplastics can penetrate the chorion of developing zebrafish, accumulate in the tissues, and affect physiology and behavior, potentially affecting organismal fitness in contaminated aquatic ecosystems.
Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother-neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother-neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5-100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother-fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14-20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
Copine 1 (CPNE1) is a well-known phospholipid binding protein in plasma membrane of various cell types. In brain cells, CPNE1 is closely associated with AKT signaling pathway, which is important for neural stem cell (NSC) functions during brain development. Here, we investigated the role of CPNE1 in the regulation of brain NSC functions during brain development and determined its underlying mechanism. In this study, abundant expression of CPNE1 was observed in neural lineage cells including NSCs and immature neurons in human. With mouse brain tissues in various developmental stages, we found that CPNE1 expression was higher at early embryonic stages compared to postnatal and adult stages. To model developing brain in vitro, we used primary NSCs derived from mouse embryonic hippocampus. Our in vitro study shows decreased proliferation and multi-lineage differentiation potential in CPNE1 deficient NSCs. Finally, we found that the deficiency of CPNE1 downregulated mTOR signaling in embryonic NSCs. These data demonstrate that CPNE1 plays a key role in the regulation of NSC functions through the activation of AKT-mTOR signaling pathway during brain development.
This study investigated the direct and indirect toxic effects of microplastics and nanoplastics toward zebrafish (Danio rerio) larvae locomotor activity. Results showed that microplastics alone exhibited no significant effects except for the upregulated zfrho visual gene expression; whereas nanoplastics inhibited the larval locomotion by 22% during the last darkness period, and significantly reduced larvae body length by 6%, inhibited the acetylcholinesterase activity by 40%, and upregulated gfap, α1-tubulin, zfrho and zfblue gene expression significantly. When co-exposed with 2 μg/L 17 α-ethynylestradiol (EE2), microplastics led to alleviation on EE2's inhibition effect on locomotion, which was probably due to the decreased freely dissolved EE2 concentration. However, though nanoplastics showed stronger adsorption ability for EE2, the hypoactivity phenomenon still existed in the nanoplastics co-exposure group. Moreover, when co-exposed with a higher concentration of EE2 (20 μg/L), both plastics showed an enhanced effect on the hypoactivity. Principal component analysis was performed to reduce data dimensions and four principal components were reconstituted in terms of oxidative stress, body length, nervous and visual system related genes explaining 84% of total variance. Furthermore, oxidative damage and body length reduction were evaluated to be main reasons for the hypoactivity. Therefore, nanoplastics alone suppressed zebrafish larvae locomotor activity and both plastic particles can change the larvae swimming behavior when co-exposed with EE2. This study provides new insights into plastic particles' effects on zebrafish larvae, improving the understanding of their environmental risks to the aquatic environment.
Monitoring plastic ingestion in marine biota is a difficult task, especially regarding ubiquitous microplastics (particles of <5 mm). Due to their microscopic size, evidence for microplastic ingestion is often limited to laboratory studies. The following review provides a comparison and assessment of different microplastic ingestion monitoring procedures. Emphasis is given to the most important steps of current monitoring practice: (1) selecting suitable indicator species, (2) sampling and sample processing, (3) analytical procedures and (4) the prevention of secondary contamination of the sample. Moreover, an overview on ingestion records of microplastics by different marine feeding guilds is presented, including filter, suspension and deposit feeders as well as predators and scavengers. Lastly, monitoring processes are addressed critically in terms of their suitability for achieving the aims of an appropriate monitoring programme. Recommendations for future research priorities are presented with a focus on the necessity of standardised and comparable monitoring procedures in microplastic detection.
Developmental exposure to bisphenol A (BPA) has been linked to impaired glucose homeostasis and pancreatic function in adulthood, which has been hypothesized to result from the disruption of pancreatic β-cell development at early life. Here we evaluated whether maternal BPA exposure disrupts β-cell development and glucose tolerance and the role of epigenetic modifications of key regulator in this process. We found that maternal exposure to BPA (10 μg kg⁻¹ d⁻¹) reduced the pancreatic β-cell mass and the expression of pancreatic and duodenal homeobox 1 (Pdx1) at birth, as well as the expression of Pdx1 at gestational day (GD) 15.5. In parallel with the decreased expression of Pdx1, histones H3 and H4 deacetylation, along with demethylation of histone 3 lysine 4 (H3K4) and methylation of histone 3 lysine 9 (H3K9), were found at the promoter of Pdx1, while no significant changes in DNA methylation status were detected at this region. Moreover, these alterations were observed in adult life along with impaired glucose tolerance. We conclude that maternal exposure to BPA reduces pancreatic β-cell mass at birth by reducing PDX1⁺ progenitors during fetal development through altering the histone modifications of Pdx1, which can be propagated to later life and increase the susceptibility to glucose intolerance.
Regulated mechanisms of stem cell maintenance are
key to preventing stem cell depletion and aging. While
mitochondrial morphology plays a fundamental role
in tissue development and homeostasis, its role in
stem cells remains unknown. Here, we uncover that
mitochondrial dynamics regulates stem cell identity,
self-renewal, and fate decisions by orchestrating a
transcriptional program. Manipulation of mitochondrial
structure, through OPA1 or MFN1/2 deletion,
impaired neural stem cell (NSC) self-renewal, with
consequent age-dependent depletion, neurogenesis
defects, and cognitive impairments. Gene expression
profiling revealed ectopic expression of the Notch
self-renewal inhibitor Botch and premature induction
of transcription factors that promote differentiation.
Changes in mitochondrial dynamics regulate stem
cell fate decisions by driving a physiological reactive
oxygen species (ROS)-mediated process, which
triggers a dual program to suppress self-renewal
and promote differentiation via NRF2-mediated
retrograde signaling. These findings reveal mitochondrial
dynamics as an upstream regulator of
essential mechanisms governing stem cell selfrenewal
and fate decisions through transcriptional
programming.
Since their ubiquity in the ocean and marine organisms was first revealed, global concern about microplastics has grown considerably. The North Pacific Ocean and the adjacent marginal seas have high levels of microplastic contamination compared with the global average. This special issue on microplastics was organized by the North Pacific Marine Science Organization to share information on microplastic pollution in the North Pacific region. The special issue highlights high levels of contamination in the North Pacific both on shorelines and at the sea surface. Particularly high levels of contamination were reported on the western and southern coasts of Korea. Sources, including sewage discharge, aquaculture, and shipyards, were implicated. With the direction and energy of surface winds and currents have an important influence on shoreline patterns of distribution. The special issue also demonstrates potential for ingestion of microplastic by small planktonic organisms at the base of the food chain. A wide range of chemicals are associated with plastic debris and concerns are expressed about the potential for these chemicals to transfer to biota upon ingestion. As an introduction to the topic, this paper provides a brief background on microplastic contamination, highlights some key research gaps, and summarizes findings from the articles published in this issue.
