Role of inflammatory response in benzo[a]pyrene-induced noradrenergic axon degeneration in mouse brain

Abstract

Environmental pollution is a major contributor to neurotoxicity and could explain various nervous system dysfunctions. The polycyclic aromatic hydrocarbon (PAH) benzo[a]pyrene (B[a]P) is widely present in the environment, including air polluted with combustion or cigarette smoke, and considered to be involved in the development of neurodegenerative disorders. Our previous study demonstrated that B[a]P decreased noradrenergic axon density and upregulated proinflammatory cytokines in the mouse brain. The aim of this study was to explore the hypothesis that B[a]P induced neurodegeneration through signals related to inflammatory response in the brain and that sulforaphane (SFN), a naturally present antioxidant and anti-inflammatory compound, can protect against B[a]P-induced neurotoxicity. Adult male mice (C57Bl/6JJcl) were exposed to B[a]P at 0, 0.87, 2.74 or 8.67 µg which is approximately equivalent to (0.037,0.117 and 0.37 mg/kg) by pharyngeal aspiration once a week, with subcutaneous injection of SFN at 0 or 25 mg/kg body weight daily for 4 weeks. Neurotoxicity was evaluated by morphological examination of noradrenergic axon density and the positive stained Iba-1 microglia in the hippocampal areas CA1 and CA3. Moreover, we also analyzed the expression of various genes in the same tissues. At 8.67 µg, B[a]P significantly increased brain weight. Sulforaphane protected against B[a]P-induced neurotoxicity, including brain weight gain, decreased noradrenergic axon density, and microglial activation in the hippocampus. Sulforaphane also suppressed B[a]P-induced upregulation of Nf-κB and Il-6. These findings demonstrate that SFN effectively protected against B[a]P-induced neuroinflammation and axonal degeneration and suggest that B[a]P-induced neurodegeneration is mediated through brain inflammatory response.