Stimulation of nicotinic acetylcholine receptors protects motor neurons

被引:41
作者
Nakamizo, T
Kawamata, J
Yamashita, H
Kanki, R
Kihara, T
Sawada, H
Akaike, A
Shimohama, S
机构
[1] Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Fac Med, Horizontol Med Res Org, Sakyo Ku, Kyoto 6068501, Japan
[3] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Sakyo Ku, Kyoto 6068501, Japan
基金
日本学术振兴会;
关键词
amyotrophic lateral sclerosis; nicotine; nicotinic acetylcholine receptor; acetylcholinesterase inhibitor; galantamine; spinal cord; motor neuron;
D O I
10.1016/j.bbrc.2005.03.115
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The present study demonstrated that administration of nicotine prevented glutamate-induced motor neuronal death in primary cultures of the rat spiral cord. The nicotine-induced neuroprotection was inhibited by either dihydro-beta-erythroidin (DHPE) or alpha-bungarotoxin (alpha BT), suggesting that it is mediated through both alpha 4 beta 2 and alpha 7 nicotinic acetylcholine receptors (nAChRs). Both alpha 4 beta 2 and alpha 7 nAChRs were identified on rat spinal motor neurons by immunohistochemical methods. We also demonstrated that galantamine, an acetylcholinesterase inhibitor with allosteric nAChR-potentiating ligand properties, prevented glutamate-induced motor neuronal death. These results suggest that stimulation of nAChR may be used as a treatment for ALS. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:1285 / 1289
页数:5
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