title: Neuroprotective effect of nicotine on dopaminergic neurons by anti-inflammatory action.
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 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.
authors.affiliation: Department of Neurology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Hyun Jung
authors.initials: HJ
authors.lastname: Park
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
authors.forename: Young Whan
authors.initials: YW
authors.lastname: Ahn
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Choi
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Lee
authors.forename: Eun S
authors.initials: ES
authors.lastname: Chung
authors.forename: Byung Kwan
authors.initials: BK
authors.lastname: Jin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents; D002038:Bungarotoxins / Q000494:pharmacology; D002452:Cell Count; D018920:Coculture Techniques; D004298:Dopamine / Q000502:physiology*; D007150:Immunohistochemistry; D008070:Lipopolysaccharides / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D017628:Microglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D009538:Nicotine / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D002038:Bungarotoxins; D008070:Lipopolysaccharides; D018696:Neuroprotective Agents; D018733:Nicotinic Antagonists; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine