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: 1.34). 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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    • "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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    • "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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    • "TNFα is a "potent" pro-inflammatory cytokine elevated in both AD and PD patients, where it is implicated to play a causal role in neurotoxicity [45]. Consistent with previous reports on short term and high exposures to air pollution [18,28,46] and chronic human studies [14], here we show a general pro-inflammatory response in the brain with subchronic DE exposure, which we propose may be due in large part to a systemic/peripheral effect that reaches the entire brain, rather than solely through the olfactory bulb, a favored pathway of PM entry into the brain [47,48]. This is evidenced by the fact that the olfactory bulb showed a blunted TNFα response when compared to other regions and TNFα levels were elevated in most regions tested, with the exception of the cerebellum (Figure 1). "
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