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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.
MeSH terms
AnimalsAnimals, NewbornAnti-Inflammatory Agents*Bungarotoxins/pharmacologyCell CountCoculture TechniquesDopamine/physiology*ImmunohistochemistryLipopolysaccharides/pharmacologyMesencephalon/cytologyMesencephalon/drug effectsMesencephalon/pathologyMicroglia/drug effectsNeurons/drug effects*Neuroprotective Agents*Nicotine/pharmacology*Nicotinic Antagonists/pharmacologyNitric Oxide/metabolismParkinson Disease/metabolismParkinson Disease/pathologyParkinson Disease/prevention & control*RatsRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionTumor Necrosis Factor-alpha/metabolismTyrosine 3-Monooxygenase/metabolism
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Neurology
Journal Papers > Research Organization > BK21
Journal Papers > School of Medicine / Graduate School of Medicine > Neurosurgery
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > Research Organization > Institute for Medical Sciences
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