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February 2011 - March 2012
January 2007 - January 2016
Publications
Publications (239)
Psychoactive substances during pregnancy and lactation is a key problem in contemporary society, causing social, economic, and health disturbance. In 2010, about 30 million people used opioid analgesics for non-therapeutic purposes, and the prevalence of opioids use during pregnancy ranged from 1% to 21%, representing a public health problem. This...
We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio i...
Fatigue is a common symptom of Parkinson’s disease that compromises significantly the patients’ quality of life. Despite that, fatigue has been under-recognized as symptom, its pathophysiology remains poorly understood, and there is no adequate treatment so far. Parkinson’s disease is characterized by the progressive loss of midbrain dopaminergic n...
N-methyl D-aspartate (NMDA) administered at subtoxic dose plays a protective role against neuronal excitotoxicity, a mechanism described as preconditioning. Since the activation of adenosinergic receptors influences the achievement of NMDA preconditioning in the hippocampus, we evaluated the potential functional interplay between adenosine A1 and A...
Chemotherapy-Induced Peripheral Neuropathy (CIPN) is a common, difficult-to-treat, and dose-limiting side effect associated with Oxaliplatin (OXA) treatment. In this study, we evaluated the effect of three antioxidants - namely N-acetylcysteine, α-lipoic acid and vitamin E – upon nociceptive parameters and antitumor efficacy of OXA in a tumor-beari...
Neuroinflammation affects dopamine metabolism and produces a set of symptoms known as sickness behavior, including fever, anhedonia, anorexia, weight loss, decreased sociability and mobility, and cognitive impairment. Motor and cognitive impairments related to sickness behavior are associated with dopamine (DA) metabolism imbalance in the prefronta...
Physical exercise attenuates the development of L-DOPA-induced dyskinesia (LID) in 6-hydroxydopamine-induced hemiparkinsonian mice through unknown mechanisms. We now tested if exercise normalizes the aberrant corticostriatal neuroplasticity associated with experimental murine models of LID. C57BL/6 mice received two unilateral intrastriatal injecti...
Obesity represents a risk factor for metabolic syndrome and cardiovascular and psychiatric disorders. Excessive caloric intake, particularly in dietary fats, is an environmental factor that contributes to obesity development. Thus, the observation that switching from long-standing dietary obesity to standard diet (SD) can ameliorate the high-fat di...
Recent evidence suggests that young rodents submitted to high fructose (FRU) diet develop metabolic, and cognitive dysfunctions. However, it remains unclear whether these detrimental effects of FRU intake can also be observed in middle-aged mice. Nine months-old C57BL/6 female mice were fed with water (Control) or 10% FRU in drinking water during 1...
Propolis consists of a honeybee product, with a complex mix of substances that have been widely used in traditional medicine. Among several compounds present in propolis, caffeic acid phenethyl ester (CAPE), and pinocembrin emerge as two principal bioactive compounds, with benefits in a variety of body systems. In addition to its well‐explored phar...
Neural stem cells can generate new neurons in the mouse adult brain in a complex multistep process called neurogenesis. Several factors regulate this process, including neurotransmitters, hormones, neurotrophic factors, pharmacological agents, and environmental factors. Purinergic signaling, mainly the adenosinergic system, takes part in neurogenes...
Attention deficit hyperactivity disorder (ADHD) is a prevalent and disabling disorder, mainly characterized by hyperactivity, inattention, and impulsivity, but also by olfactory and memory impairments that frequently persist throughout lifetime. The pathophysiology of ADHD is complex, involving several brain regions and neural pathways including al...
Diagnosis of Parkinson's disease (PD) remains a challenge in clinical practice, mostly due to lack of peripheral blood markers. Transcriptomic analysis in blood samples has emerged as a potential means to identify biomarkers and gene signatures of PD. In this context, classification algorithms can assist to detect data patterns such as phenotypes a...
Degeneration of the locus coeruleus (LC), the main source of cerebral noradrenaline (NA), has been reported in diverse neurodegenerative diseases, including Parkinson’s diseases (PD). There is increasing evidence indicating the role of NA deficiency in the prefrontal cortex (PFC) and the development of early cognitive impairments in PD. Here, we ev...
Exposure to fungicide ziram (zinc dimethyldithiocarbamate) has been associated with increased incidence of Parkinson’s disease (PD). We recently demonstrated that the intranasal (i.n.) administration of sodium dimethyldithiocarbamate (NaDMDC, a more soluble salt than ziram) induces PD-like behavioral and neurochemical alterations in mice. We now in...
Omega-3-enriched fish oil (FO) and caloric restriction (CR) are nutritional therapeutic approaches that exert an important impact on brain function, behavior, memory, and neuroprotection. Here, we investigate the synergic effects of both therapeutic approaches combined (CR + FO) on behavior (memory, anxiety-like behavior, antidepressant-like behavi...
Fear is a conscious state caused by exposure to real or imagined threats that trigger stress responses that affect the body and brain, particularly limbic structures. A sub-group of patients with mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) have seizures with fear, which is called ictal fear (IF), due to epileptic activi...
The systemic administration of low reserpine (RES) doses (0.1 - 1.0 mg/kg) has been proposed as a valuable rat model for the study of non-motor symptoms of Parkinson's disease (PD). Here, we investigated the temporal-dependent effects of RES (1 mg/kg, s.c.) on short-term memory and locomotion, as well as, the levels of dopamine, serotonin and its m...
Although the benefits of moderate intake of red wine in decreasing incidence of cardiovascular diseases associated to hypercholesterolemia are well recognized, there are still widespread misconceptions about its effects on the hypercholesterolemia-related cognitive impairments. Herein we investigated the putative benefits of regular red wine consum...
Familial hypercholesterolemia (FH) is a genetic disorder caused by dysfunction of low density lipoprotein receptors (LDLr), resulting in elevated plasma cholesterol levels. FH patients frequently exhibit cognitive impairment, a finding recapitulated in LDLr deficient mice (LDLr-/-), an animal model of FH. In addition, LDLr-/- mice are more vulnerab...
Introduction: Parkinson's disease (DP) is the second most common neurodegenerative disease and is characterized as a motor neurodegenerative disease. However, among the non-motor symptoms, depression is the most common and the one that most impact the
patient’s quality of life. Depression in PD is more prevalent in women, its neurobiological basis...
Parkinson's disease (DP) is the second most common neurodegenerative disease and is
characterized as a motor neurodegenerative disease. However, among the non-motor symptoms, depression is the most common and the one that most impact the patient’s quality of life. Depression in PD is more prevalent in women, its neurobiological basis remains poorly...
The attention deficit/hyperactivity disorder (ADHD) affects 5% of children and adolescents worldwide, and is known by its cardinal symptoms: hyperactivity, inattention and impulsivity. Remarkably, ADHD subjects are more susceptible to develop psychiatric disorders such as depression. Previous non-clinical and clinical studies have demonstrated the...
The host evolves redundant mechanisms to preserve physiological processing and homeostasis. These functions range from sensing internal and external threats, creating a memory of the insult and generating reflexes which aim to resolve inflammation. Impairment in such functioning leads to chronic inflammatory diseases. By interacting through a commo...
The dorsolateral striatum (DLS) processes motor and non-motor functions and undergoes extensive dopaminergic degeneration in Parkinson's disease (PD). Beyond the nigrostriatal pathway, dopaminergic degeneration also affects other brain areas including the pre-frontal cortex (PFC) and hippocampus, which have been associated with the appearance of an...
The Spontaneously Hypertensive Rat (SHR) has been proposed as a good model to study the pathways related to neurodegenerative diseases and glucose intolerance. Our research group developed the SLA16 (SHR.LEW-Anxrr16) congenic strain, which is genetically identical to the SHR strain, except for a locus on chromosome 4 (DGR). We applied in silico ana...
Exercise can act as a disease-modifying agent in Parkinson's disease (PD), and we have previously demonstrated that voluntary exercise in running wheels during 2 weeks normalizes striatopallidal dopaminergic signaling and prevents the development of L-DOPA-induced dyskinesia (LID) in C57BL/6 mice. We now tested whether LID in Swiss albino mice coul...
Noradrenergic degeneration in the locus coeruleus (LC) seems a convergent neuropathological marker of different neurodegenerative diseases. Herein, we investigated the temporal development of apoptotic signaling activation in the LC, noradrenergic dysfunction and behavioral impairments in rats following the noradrenergic lesion of the LC. For this...
Ketamine is used in clinical practice as an anesthetic that pharmacologically modulates neurotransmission in postsynaptic receptors, such as NMDA receptors. However, widespread recreational use of ketamine in “party drug” worldwide since the 1990s quickly spread to the Asian orient region. Thus, this study aimed at investigating the behavioral and...
Chronic metabolic alterations may represent a risk factor for the development of cognitive impairment, dementia, or neurodegenerative diseases. Hyperglycemia and obesity are known to imprint epigenetic markers that compromise the proper expression of cell survival genes. Here, we showed that chronic hyperglycemia (60 days) induced by a single intra...
There is a mutual relationship between metabolic and neurodegenerative diseases. However, the causal relationship in this crosstalk is unclear and whether Parkinson’s disease (PD) causes a posterior impact on metabolism remains unknown. Considering that, this study aimed to evaluate the appearance of possible changes in metabolic homeostasis due to...
Olfactory dysfunction seems to occur earlier than classic motor and cognitive symptoms in many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease (AD). Thus, the use of the olfactory system as a clinical marker for neurodegenerative diseases is helpful in the characterization of prodromal stages of these diseases...
Recent studies on interactions between striatal adenosine and dopamine and one of its main targets, the adenosine A2A receptor–dopamine D2 receptor (A2AR–D2R) heteromer, have provided a better understanding of the mechanisms involved in the psychostimulant effects of caffeine and have brought forward new data on the mechanisms of operation of class...
Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common chronic childhood-onset psychiatric disorders. ADHD persists in many cases into adulthood, the occurrence which
is associated with attentional deficits, hyperactivity, and/or cognitive impulsiveness. A primary role of disturbances in frontocortical dopaminergic ne...
Depression is a highly prevalent and debilitating non-motor symptom observed during the early stages of Parkinson’s disease (PD). Although PD prevalence is higher in men, the depressive symptoms in PD are more common in women. Therefore, the aim of this study was to investigate the development of anhedonic- and depressive-like behaviors in male and...
The neonatal exposure to general anesthetics has been associated with neuronal apoptosis and dendritic spines morphologic changes in the developing brain. Ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used in pediatric patients to induce general anesthesia, analgesia, and perioperative sedation. In the presen...
Tetrahydrobiopterin (BH4) is synthesized by the combined action of three metabolic pathways, namely de novo synthesis, recycling, and salvage pathways. The best-known function of BH4 is its mandatory action as a natural cofactor of the aromatic amino acid hydroxylases and nitric oxide synthases. Thus, BH4 is essential for the synthesis of nitric ox...
Depression is one of the most common psychiatric symptoms in Alzheimer's disease (AD), and several studies have shown that oxidative stress plays a key role in the etiopathology of both AD and depression. Clinical studies indicate reduced efficacy of the current antidepressants for the treatment of depression in AD. In this regard, agmatine emerges...
Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we...
Alzheimer's disease (AD) is characterized by progressive synaptic dysfunction and neuronal lost in specific brain areas including hippocampus, resulting in memory/learning deficits and cognitive impairments. In addition, non-cognitive symptoms are reported in AD patients, such as anxiety, apathy and depressed mood. The current antidepressant drugs...
Binge-like ethanol intake (BEI) is a socioeconomical problem among adolescents and increasingly affects women. BEI can leave a long-term imprint in the brain, but it is unknown if its effect on cognition and anxiety is cumulative on repeated binge-ethanol episodes. We now submitted female Wistar rats to repeated cycles of binge-like ethanol treatme...
Atorvastatin is a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor with cholesterol-lowering, anti-inflammatory, and antioxidant properties. Increasing evidence show atorvastatin acts as a protective agent against insults in the central nervous system (CNS). The regular use of statins has been associated with a reduced risk of Pa...
Systemic inflammation triggered by lipopolysaccharide (LPS) administration disrupts blood–brain barrier (BBB) homeostasis in animal models. This event leads to increased susceptibility of several encephalic structures to potential neurotoxicants present in the bloodstream. In this study, we investigated the effects of alternate intraperitoneal inje...
The primary etiology of Parkinson's disease (PD) remains unclear, but likely reflects a combination of genetic and environmental factors. Exposure to some pesticides, including ziram (zinc dimethyldithiocarbamate), is a relevant risk factor for PD. Like some other environmental neurotoxicants, we hypothesized that ziram can enter the central nervou...
The interaction between genes and environmental factors has been explored in the study of the development of attention-deficit hyperactivity disorder (ADHD), one of the most prevalent childhood psychiatric diseases. The occurrence of ADHD is typically associated with poor academic performance reflecting attentional deficits, learning difficulties a...
Ketamine acts as an N-methyl-d-aspartate (NMDA) receptor antagonist that was originally synthesized for use as a dissociative anesthetic, and remains widely used for this clinical application. More recently, the recreational use of ketamine, particularly in individuals who frequent nightclubs and have adopted the “rave culture” has been reported. T...
Alcohol-related brain damage (ARBD) and fetal alcohol spectrum disorders (FASDs) include a set of neuropsychiatric disorders that may be caused by alcohol-use disorders. Among these neurological syndromes, the alcohol exposure can occur in an indirect (FASD) or direct (ARBD) pathway and produce its toxic effects through various mechanism, as neurot...
Background:
Ursolic acid has been shown to display antidepressant-like effects in mice through the modulation of monoaminergic systems. In this study, we sought to investigate the involvement of signaling pathways on the antidepressant-like effects of ursolic acid.
Methods:
Mice were treated orally with ursolic acid (0.1mg/kg) and, 45min later t...
Periodontitis is an oral chronic infection/inflammatory condition, identified as a source of mediators of inflammation into the blood circulation, which may contribute to exacerbate several diseases. There is increasing evidence that inflammation plays a key role in the pathophysiology of Alzheimer’s disease (AD). Although inflammation is present i...
Interictal hypometabolism is commonly measured by 18-fluoro-deoxyglucose Positron Emission Tomography (FDG-PET) in the temporal lobe of patients with mesial temporal lobe epilepsy (MTLE-HS). Left temporal lobe interictal FDG-PET hypometabolism has been associated with verbal memory impairment, while right temporal lobe FDG-PET hypometabolism is ass...
(1) Objectives: Epilepsy disorder is likely to increase with aging, leading to an increased incidence of comorbidities and mortality. In spite of that, there is a lack of information regarding this issue and little knowledge of cognitive and emotional responses in aging subjects following epileptogenesis. We investigated whether and how aging distr...
Amyloid-beta (Aβ) peptides are the major neuropathological hallmarks related with Alzheimer’s disease (AD). Aβ peptides trigger several biochemical mechanisms of neurotoxicity, including neuroinflammation and glutamatergic neurotransmission impairment. Guanosine is the endogenous guanine-derived nucleoside that modulates the glutamatergic system an...
We have previously demonstrated that maternal exposure to glyphosate-based herbicide (GBH) leads to glutamate excitotoxicity in 15-day-old rat hippocampus. The present study was conducted in order to investigate the effects of subchronic exposure to GBH on some neurochemical and behavioral parameters in immature and adult offspring. Rats were expos...
Tardive dyskinesia (TD) is a serious motor side effect that may appear after long-term treatment with neuroleptics and mostly mediated by dopamine D2 receptors (D2Rs). Striatal D2R functioning may be finely regulated by either adenosine A2A receptor (A2AR) or angiotensin receptor type 1 (AT1R) through putative receptor heteromers. Here, we examined...
Parkinson's disease (PD) prodromic stages comprise neuropsychiatric perturbations that critically compromise patient's quality of life. These non-motor symptoms (NMS) are associated with exacerbated innate immunity, a hallmark of overt PD. Physical exercise (PE) has the potential to improve neuropsychiatric deficits and to modulate immune network i...
Ghrelin is a metabolic hormone that has neuroprotective actions in a number of neurological conditions including Parkinson's disease (PD), stroke and traumatic brain injury. Acyl ghrelin treatment in vivo and in vitro also shows protective capacity in Alzheimer's disease (AD). In this study, we used ghrelin knockout (KO) and their wildtype (WT) lit...
Alcohol-induced brain disorders have been reported for many decades. Ethanol (EtOH) presents amphiphilicity properties that permit the fluidibility across the biological barriers. The EtOH kinetics depends on the gender and age that elicit different brain susceptibility damage. The exact mechanisms that underlie such central nervous system (CNS) di...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by non-motor and motor disabilities. This study investigated whether succinobucol (SUC) could mitigate nigrostriatal injury caused by intranasal 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration in mice. Moreover, the effects of SUC against MPTP-induced behavior...
Moderate traumatic brain injury (TBI) might increase the vulnerability to neuronal neurodegeneration, but the basis of such selective neuronal susceptibility has remained elusive. In keeping with the disruption of the blood-brain barrier (BBB) caused by TBI, changes in BBB permeability following brain injury could facilitate the access of xenobioti...
Parkinson’s disease (PD), the second most common neurodegenerative disease, is a multisystem disorder clinically
diagnosed by the motor symptoms related to dopaminergic neurodegeneration in the nigrostriatal pathway. However, PD is no
longer considered a pure motor disease. The presence of smell loss and the pathological involvement of olfactory pa...
Another important hormone is 17β-estradiol (E2), which, in addition to its multiple actions throughout the body and brain, exerts neuroprotective effects in both acute and chronic neurodegenerative diseases such as cerebral ischemia, traumatic brain injury, AD, and PD. R. Thakkar and colleagues investigated whether 17β-estradiol (E2), acting via th...
Objective:
Machado-Joseph disease (MJD) is a neurodegenerative spinocerebellar ataxia (SCA) associated with an expanded polyglutamine tract within ataxin-3 for which there is currently no available therapy. We previously showed that caffeine, a non-selective adenosine receptor antagonist, delays the appearance of striatal damage resulting from exp...
The potential efficacy of cannabinoid receptor ligands for the treatment of epilepsy remains controversial; cannabis components that act via cannabinoid type 1 (CB1) receptors produce anticonvulsant effects in animal models despite treatment with the CB receptor agonist reliably inducing convulsions in various species. Moreover, the potential role...
Here we showed that persistent hyperglycemia, a hallmark of some chronic metabolic diseases promotes epigenetic changes in the CNS that convey in higher susceptibility to neurodegeneration, compromising learning and memory. In order to investigate of impact of chronic hyperglycemia (10 or 60 days) on these neurochemical and behavioral parameters, W...