Nicotine Prevents Experimental Parkinsonism in Rodents and Induces Striatal Increase of Neurotrophic Factors
Nicotine Prevents Experimental Parkinsonism in Rodents and Induces Striatal Increase of Neurotrophic Factors
复制标题
尼古丁预防啮齿动物实验性帕金森病并诱导纹状体神经营养因子增加
DOI：
10.1046/j.1471-4159.1998.71062439.x
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发表时间：
1998
影响因子：
4.7
通讯作者：
G. Corsini
中科院分区：
文献类型：
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作者：
R. Maggio;M. Riva;F. Vaglini;F. Fornai;R. Molteni;M. Armogida;G. Racagni;G. Corsini
摘要：吸烟对帕金森病风险具有明显的保护作用，这一反复发现是这种疾病流行病学中为数不多的一致结果之一。在烟草烟雾产生的众多物质中，尼古丁是迄今为止研究最广泛的物质。尼古丁是一种天然生物碱，对中枢神经系统有相当大的刺激作用。其对CNS的作用是通过激活神经元异聚乙酰胆碱门控离子通道受体（nAChR，也称为烟碱乙酰胆碱受体）介导的。在本研究中，我们描述了（-）-尼古丁在两种帕金森病动物模型中的神经保护作用：二乙基二硫代氨基甲酸酯诱导的小鼠1-甲基-4-苯基-1，2，3，6-四氢吡啶毒性增强和甲基苯丙胺诱导的大鼠和小鼠神经毒性。（−）-尼古丁的神经保护作用与非竞争性NMDA受体拮抗剂（+）-MK-801非常相似。在平行实验中，我们发现（-）-尼古丁诱导大鼠纹状体中的碱性成纤维细胞生长因子-2（FGF-2）和脑源性神经营养因子。nAChR拮抗剂美加明阻止了（-）-尼古丁对FGF-2诱导的影响。我们还发现（+）-MK-801能够诱导纹状体中的FGF-2。由于营养因子已被报道对多巴胺能细胞具有神经保护作用，我们的数据表明，神经营养因子的增加是（−）-尼古丁保护实验性帕金森病的可能机制。
Abstract: The repeated finding of an apparent protective effect of cigarette smoking on the risk of Parkinson's disease is one of the few consistent results in the epidemiology of this disorder. Among the numerous substances that originate from tobacco smoke, nicotine is by far the most widely studied. Nicotine is a natural alkaloid that has considerable stimulatory effects on the CNS. Its effects on the CNS are mediated by the activation of neuronal heteromeric acetylcholine‐gated ion channel receptors (nAChRs, also termed nicotinic acetylcholine receptors). In the present study, we describe the neuroprotective effects of (−)‐nicotine in two animal models of parkinsonism: diethyldithiocarbamate‐induced enhancement of 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine toxicity in mice and methamphetamine‐induced neurotoxicity in rats and mice. The neuroprotective effect of (−)‐nicotine was very similar to that of the noncompetitive NMDA receptor antagonist (+)‐MK‐801. In parallel experiments, we found that (−)‐nicotine induces the basic fibroblast growth factor‐2 (FGF‐2) and the brain‐derived neurotrophic factor in rat striatum. The effect of (−)‐nicotine on the induction of FGF‐2 was prevented by the nAChR antagonist mecamylamine. We also found that (+)‐MK‐801 was able to induce FGF‐2 in the striatum. As trophic factors have been reported to be neuroprotective for dopaminergic cells, our data suggest that the increase in neurotrophic factors is a possible mechanism by which (−)‐nicotine protects from experimental parkinsonisms.
DOI：
--
发表时间：
1991-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
P. Sonsalla;D. E. Riordan;R. Heikkila
通讯作者：
P. Sonsalla;D. E. Riordan;R. Heikkila