Neuroprotective effect of nicotine on dopaminergic neurons by anti‐inflammatory action

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Abstract
Epidemiological studies have reported that smoking is associated with a lower incidence of Parkinson's disease (PD), leading to theories that smoking in general and nicotine in particular might be neuroprotective. Recent studies suggested cholinergic anti‐inflammatory pathway‐regulating microglial activation through α7 nicotinic receptors. In the present study, we used lipopolysaccharide (LPS)‐inducedin vitroandin vivoinflammation models to investigate whether nicotine has a protective effect on the dopaminergic system through an anti‐inflammatory mechanism. Nicotine pretreatment considerably decreased microglial activation with significant reduction of tumour necrosis factor (TNF)‐α mRNA expression and TNF‐α release induced by LPS stimulation. In co‐cultures of microglia and mesencephalic neurons, nicotine pretreatment significantly decreased the loss of tyrosine hydroxylase‐immunopositive (TH‐ip) cells, approximately twice more than the LPS‐only treatment. α‐Bungarotoxin, an α7 nicotinic acetylcholine receptor subunit‐selective blocker, considerably blocked the inhibitory effects of nicotine on microglial activation and TH‐ip neuronal loss. Chronic nicotine pretreatment in rats showed that TH‐ip neuronal loss induced by LPS stimulation in the substantia nigra was dramatically decreased, which was clearly accompanied by a reduction in the formation of TNF‐α. The present study demonstrated that nicotine has a neuroprotective effect on dopaminergic neurons via an anti‐inflammatory mechanism mediated by the modulation of microglial activation. Along with various neuroprotective effects of nicotine, the anti‐inflammatory mechanism of nicotine could have a major therapeutic implication in the preventive treatment of PD.

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