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Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action.

Park, HJ | Lee, PH  | Ahn, YW  | Choi, YJ | Lee, G  | Lee, DY | Chung, ES  | Jin, BK
The European journal of neuroscience, 26(1). : 79-89, 2007
Journal Title
The European journal of neuroscience
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 alpha7 nicotinic receptors. In the present study, we used lipopolysaccharide (LPS)-induced in vitro and in vivo inflammation 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)-alpha mRNA expression and TNF-alpha 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. alpha-Bungarotoxin, an alpha7 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-alpha. 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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Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > Research Organization > BK21
Journal Papers > Research Organization > Institute for Medical Sciences
Ajou Authors
안, 영환  |  이, 광  |  이, 필휴  |  정, 은숙  |  진, 병관
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