Stimulation of nicotinic acetylcholine receptors protects motor neurons.
The present study demonstrated that administration of nicotine prevented glutamate-induced motor neuronal death in primary cultures of the rat spinal cord. The nicotine-induced neuroprotection was inhibited by either dihydro-beta-erythroidin (DHbetaE) or alpha-bungarotoxin (alphaBT), suggesting that it is mediated through both alpha4beta2 and alpha7 nicotinic acetylcholine receptors (nAChRs). Both alpha4beta2 and alpha7 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.
Nakamizo
Tomoki
T
Department of Neurology, Graduate School of Medicine, Kyoto University, Sakyoku, Kyoto 606-8507, Japan.
Kawamata
Jun
J
Yamashita
Hirofumi
H
Kanki
Rie
R
Kihara
Takeshi
T
Sawada
Hideyuki
H
Akaike
Akinori
A
Shimohama
Shun
S
D000494:Allosteric Regulation; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D005333:Fetus / Q000166:cytology; D005702:Galantamine / Q000494:pharmacology; D018698:Glutamic Acid / Q000633:toxicity; D007150:Immunohistochemistry; D009046:Motor Neurons / Q000187:drug effects* / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; D002800:Cholinesterase Inhibitors; C579165:Chrna7 protein, rat; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D005702:Galantamine; D004079:Dihydro-beta-Erythroidine; D018698:Glutamic Acid; D009538:Nicotine