Article

Particulate Matter Induced Enhancement of Inflammatory Markers in the Brains of Apolipoprotein E Knockout Mice

Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, California 91766-1854, USA.
Journal of Nanoscience and Nanotechnology (Impact Factor: 1.56). 08/2009; 9(8):5099-104. DOI: 10.1166/jnn.2009.GR07
Source: PubMed

ABSTRACT

Exposure to air particulate matter (PM) present in urban environments have been shown to induce systemic prooxidant and proinflammatory effects in apolipoprotein E knockout (ApoE-/-) mice and proinflammatory central nervous system (CNS) effects in BALB/c mice. We hypothesize that ApoE-/- mice would exhibit a greater propensity to develop PM-induced CNS effects due to their greater susceptibility to CNS inflammation. We studied the brains of ApoE-/- mice exposed in a previous study to concentrated air particles of different sizes (fine vs. ultrafine) or filtered-air to evaluate the effect of PM exposure on the development of CNS proinflammatory effects in a genetically susceptible background. This was important because, although the use of nano-sized materials opens an exciting potential for their use as diagnostic or therapeutic tools, not much is known about the possible CNS toxicity of these particles. Neuroinflammation has been shown to exacerbate progression of neurodegeneration. Since the onset and progression of idiopathic forms of neurodegenerative disorders are likely to be multifactorial and involve gene-environment interactions, we determined the possibility of particles in ambient air pollution to enhance neuroinflammation. Our results indicate that in the brain, there was significant modulation in the activation of the transcription factors NF-kappaB and AP-1 after exposure to the ultrafine fractions. Levels of two pro-inflammatory cytokines (TNF-alpha and IL-1alpha) were also increased in the brain of exposed animals and this was independent of the size fraction of PM. Since inflammatory processes have been shown to contribute to the pathology associated with neurodegenerative diseases, it will be important to further evaluate the role ambient particles may play in the potentiation of existing CNS damage and progression of neurodegenerative disorders.

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    • "TNF is a potential pro-inflammatory mediator seen elevated in neuro-degenerative disorders and play a key role in neurotoxicity (McCoy and Tansey, 2008). Acute and chronic studies of air pollution in humans presented a common pro-inflammatory cytokine response in different brain regions (Levesque et al., 2011;Campbell et al., 2009). However, in the present study the midbrain region was more vulnerable to TNF exposure even at low concentrations especially the substania nigra region of the mid brain. "
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    ABSTRACT: Air pollution is a major problem faced globally and is seen associated with central nervous system (CNS) disorders like neuropathology and neuro-inflammation. Here, we investigated the CNS disorders as a result of sub-chronic exposure (90 days) to diesel exhaust nanoparticles (DENPs) and explored the minimal levels of DENPs needed to exhibit the early mediators of neuro-inflammation and neuropathology. Male and female wistar rats (6 rats per group) were exposed to DENPs (1/5th, 1/10th and 1/15th LC50) by inhalation for 4h per day, 5 days per week over 90 days and neurotoxicity end-points were analyzed. DENP exposure caused elevation in levels of pro-inflammatory cytokines, amyloid beta 42 (Aβ 42), reactive oxygen species (ROS), hydrogen peroxide (H2O2), nitrate (NO3(-)), nitrite (NO2(-)) and apurinic/apyrimidinic sites (AP) at varying degrees at different sections of rat brain. Hence, exposure to DENPs resulted in dose-dependent toxicity and was closely correlated to increased inflammation, DNA damage and oxidative stress.
    Full-text · Article · Sep 2015 · Environmental Toxicology and Pharmacology
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    • "Air pollutants with an aerodynamic diameter of <2.5 ␮m (PM 2.5 ) have been lately found to be related with increased cardiovascular , respiratory and pro-inflammatory effects associated with death and diseases (Campbell et al., 2009). Vital two regarding adverse health effects (Donaldson et al., 2005). "
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    ABSTRACT: Air pollution has persistently been the major cause of respiratory-related illness and death. Environmental pollutants such as diesel and petrol exhaust particles (PEPs) are the major contributors to urban air pollution. The aim of the present study was to characterize and investigate the in vitro cytotoxicity, oxidative stress, DNA damage and inflammation induced by PEPs. Cultured type II epithelium cells (human A549 lung cells) and alveolar macrophages (murine RAW 264.7 cells) were exposed to control, vehicle control and to different concentrations of PEPs for up to 24h. Each treatment was evaluated by cell viability, cytotoxicity, oxidative stress, DNA damage and inflammatory parameters. Overall in vitro studies demonstrated that both cell lines showed similar patterns in response to the above studies induced by petrol exhaust nanoparticles (PENPs). Vehicle control showed no changes compared with the control. In both cell lines, significant changes at the dose of 20 and 50μg/mL (A549 cell lines) and 10and 20μg/mL (macrophages) for PENPs were found. The reactive oxygen species production in both cell lines shot up in minutes, reached the maximum within an hour and came down after 4h. Hence, exposure to PENPs resulted in dose-dependent toxicity in cultured A549 cells and RAW 264.7 cells and was closely correlated to increased oxidative stress, DNA damage and inflammation.
    Full-text · Article · Aug 2014 · Environmental Toxicology and Pharmacology
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    • "A very critical component of air pollution exposure is neuroinflammation [8, 50–52]. MCMA young urbanites exhibit an important frontal imbalance in genes essential for inflammation, innate and adaptive immune responses, oxidative stress, cell proliferation and apoptosis, when compared to age-matched residents in low pollution cities [30]. "
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    ABSTRACT: Chronic exposure to particulate matter air pollution is known to cause inflammation leading to respiratory- and cardiovascular-related sickness and death. Mexico City Metropolitan Area children exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, and innate and adaptive immune responses. Early dysregulated neuroinflammation, brain microvascular damage, production of potent vasoconstrictors, and perturbations in the integrity of the neurovascular unit likely contribute to progressive neurodegenerative processes. The accumulation of misfolded proteins coincides with the anatomical distribution observed in the early stages of both Alzheimer's and Parkinson's diseases. We contend misfolding of hyperphosphorylated tau (HP π ), alpha-synuclein, and beta-amyloid could represent a compensatory early protective response to the sustained systemic and brain inflammation. However, we favor the view that the chronic systemic and brain dysregulated inflammation and the diffuse vascular damage contribute to the establishment of neurodegenerative processes with childhood clinical manifestations. Friend turns Foe early; therefore, implementation of neuroprotective measures to ameliorate or stop the inflammatory and neurodegenerative processes is warranted in exposed children. Epidemiological, cognitive, structural, and functional neuroimaging and mechanistic studies into the association between air pollution exposures and the development of neuroinflammation and neurodegeneration in children are of pressing importance for public health.
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