Nicotine protects cultured striatal neurones against N-methyl-D-aspartate receptor-mediated neurotoxicity.
The role of cholinergic mechanisms in N-methyl-D-aspartate (NMDA)-mediated neuronal death was investigated using mouse striatal neurones in primary culture. A 30 min exposure of striatal neurones to increasing concentrations of NMDA resulted 24 h later in dramatic neuronal degeneration as assessed by MTT staining, crystal violet incorporation and determination of microtubule-associated protein 2. The NMDA-induced neurodegeneration was strongly inhibited by the co-application of two non-selective cholinergic agonists, acetylcholine or carbachol. This protective effect appears to be mediated by nicotinic receptors since it was insensitive to the muscarinic antagonist atropine but mimicked by nicotine, nornicotine and 1,1-dimethyl-4-phenyl-piperazinium. Moreover, the nicotine-evoked neuroprotection was inhibited by the central nicotinic antagonist hexamethonium. Therefore, this study suggests that cholinergic interneurones play an important role in neuronal survival in the striatum.
Marin
P
P
Laboratoire de Neuropharmacologie, INSERM U114, Collège de France, Paris.
Maus
M
M
Desagher
S
S
Glowinski
J
J
Prémont
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002478:Cells, Cultured; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D018738:Hexamethonium / Q000494:pharmacology; D051379:Mice; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000633:toxicity; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects*; D009410:Nerve Degeneration / Q000187:drug effects; D009422:Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects
D011950:Receptors, Cholinergic; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic; D018738:Hexamethonium; D004246:Dimethylphenylpiperazinium Iodide; D016202:N-Methylaspartate; D009538:Nicotine; D002217:Carbachol; D000109:Acetylcholine