Diesel Exhaust Activates and Primes Microglia: Air Pollution, Neuroinflammation, and Regulation of Dopaminergic Neurotoxicity
Autor: | Michael J. Surace, Shannon Levesque, Michelle L. Block, Krisztian Stadler, Thomas Taetzsch, Jo Anne Johnson, Urmila P. Kodavanti, Melinda E. Lull, Prasada Rao S. Kodavanti, Alison F. Wagner, Laura Duke |
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Rok vydání: | 2011 |
Předmět: |
Male
Chemokine Health Toxicology and Mutagenesis air pollution Interleukin-1beta microglia 010501 environmental sciences Pharmacology medicine.disease_cause Rats Inbred WKY 01 natural sciences neuroinflammation Rats Sprague-Dawley chemistry.chemical_compound 0302 clinical medicine oxidative stress Chemokine CCL3 Vehicle Emissions biology Microglia Microfilament Proteins 3. Good health medicine.anatomical_structure Tumor necrosis factor alpha medicine.symptom brain Inflammation Nitric oxide 03 medical and health sciences medicine Animals Neuroinflammation 0105 earth and related environmental sciences Chemokine CX3CL1 Interleukin-6 Tumor Necrosis Factor-alpha Research Dopaminergic Neurons Calcium-Binding Proteins Public Health Environmental and Occupational Health Neurotoxicity Hydrogen Peroxide medicine.disease Rats chemistry 13. Climate action Immunology Parkinson’s disease biology.protein 030217 neurology & neurosurgery Oxidative stress |
Zdroj: | Environmental Health Perspectives |
ISSN: | 1552-9924 0091-6765 |
Popis: | Background: Air pollution is linked to central nervous system disease, but the mechanisms responsible are poorly understood. Objectives: Here, we sought to address the brain-region–specific effects of diesel exhaust (DE) and key cellular mechanisms underlying DE-induced microglia activation, neuroinflammation, and dopaminergic (DA) neurotoxicity. Methods: Rats were exposed to DE (2.0, 0.5, and 0 mg/m3) by inhalation over 4 weeks or as a single intratracheal administration of DE particles (DEP; 20 mg/kg). Primary neuron–glia cultures and the HAPI (highly aggressively proliferating immortalized) microglial cell line were used to explore cellular mechanisms. Results: Rats exposed to DE by inhalation demonstrated elevated levels of whole-brain IL-6 (interleukin-6) protein, nitrated proteins, and IBA-1 (ionized calcium-binding adaptor molecule 1) protein (microglial marker), indicating generalized neuroinflammation. Analysis by brain region revealed that DE increased TNFα (tumor necrosis factor-α), IL-1β, IL-6, MIP-1α (macrophage inflammatory protein-1α) RAGE (receptor for advanced glycation end products), fractalkine, and the IBA-1 microglial marker in most regions tested, with the midbrain showing the greatest DE response. Intratracheal administration of DEP increased microglial IBA-1 staining in the substantia nigra and elevated both serum and whole-brain TNFα at 6 hr posttreatment. Although DEP alone failed to cause the production of cytokines and chemokines, DEP (5 μg/mL) pretreatment followed by lipopolysaccharide (2.5 ng/mL) in vitro synergistically amplified nitric oxide production, TNFα release, and DA neurotoxicity. Pretreatment with fractalkine (50 pg/mL) in vitro ameliorated DEP (50 μg/mL)-induced microglial hydrogen peroxide production and DA neurotoxicity. Conclusions: Together, these findings reveal complex, interacting mechanisms responsible for how air pollution may cause neuroinflammation and DA neurotoxicity. |
Databáze: | OpenAIRE |
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