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

Hyun Jung Park, Phil Hyu Lee, Young Whan Ahn, Yun Jung Choi, Gwang Lee, Da Yong Lee, Eun S. Chung, Byung Kwan Jin

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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)-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)-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.

Original languageEnglish
Pages (from-to)79-89
Number of pages11
JournalEuropean Journal of Neuroscience
Volume26
Issue number1
DOIs
Publication statusPublished - 2007 Jul 1

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Dopaminergic Neurons
Neuroprotective Agents
Nicotine
Anti-Inflammatory Agents
Lipopolysaccharides
Tyrosine 3-Monooxygenase
Tumor Necrosis Factor-alpha
Nicotinic Receptors
Parkinson Disease
Smoking
Bungarotoxins
Microglia
Substantia Nigra
Coculture Techniques
Cholinergic Agents
Epidemiologic Studies
Inflammation
Neurons
Messenger RNA
Incidence

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Park, Hyun Jung ; Lee, Phil Hyu ; Ahn, Young Whan ; Choi, Yun Jung ; Lee, Gwang ; Lee, Da Yong ; Chung, Eun S. ; Jin, Byung Kwan. / Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. In: European Journal of Neuroscience. 2007 ; Vol. 26, No. 1. pp. 79-89.
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Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action. / Park, Hyun Jung; Lee, Phil Hyu; Ahn, Young Whan; Choi, Yun Jung; Lee, Gwang; Lee, Da Yong; Chung, Eun S.; Jin, Byung Kwan.

In: European Journal of Neuroscience, Vol. 26, No. 1, 01.07.2007, p. 79-89.

Research output: Contribution to journalArticle

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