α7-nicotinic acetylcholine receptor and mutated α-synuclein interact in motor behavior and nigrostriatal dopamine - findings with potential relevance for a protective effect of cigarette smoking and Parkinson’s disease

Le résumé fourni par la source

Parkinson’s disease (PD) occurs less frequently in cigarette smokers than in non-smokers. Assuming that nicotinic acetylcholine receptors are periodically active by activation through endogenous acetylcholine, we tested whether they act against the effect of α-synuclein, a protein relevant in PD. Transgenic mice with a human α-synuclein containing two mutations that cause familial PD were crossed with mice lacking the nicotinic α7-acetylcholine receptor. Vertical movements determined at 7 and 16 months and non-ambulatory movements at 16 months of age were significantly lower in mice with α7-acetylcholine receptor knockout if they express the mutated α-synuclein, but not in mice with α-synuclein wildtype. Striatal noradrenaline, serotonin and dopamine levels did not differ between the four groups of mice at 21 months however striatal dopamine turnover was significantly higher in mice without than with α7-acetylcholine receptor. Stereological counts of nigral cells positive for tyrosine hydroxylase in the left and right hemisphere at 21 months revealed that asymmetry was also significantly higher in mice without than with α7-acetylcholine receptor. In conclusion, up to the age of 16 months there was no obvious PD behavior, however absence of the α7-acetylcholine receptor generally reduced several features of motor behavior and showed a statistically significant interaction between α7-acetylcholine receptor and mutated α-synuclein. The asymmetry of nigral cell counts and the increased striatal dopamine turnover suggest a stressed nigrostriatal system in mice without α7-acetylcholine receptor and that the neuroprotective effect of smoking might at least partly be mediated by the nicotine in the cigarettes acting via α7-acetylcholine receptors.

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