Guan Zhi-Zhong, Nordberg Agneta, Mousavi Malahat, Rinne Juha O, Hellström-Lindahl Ewa
Karolinska Institutet, Department of Clinical Neuroscience, Occupational Therapy and Elderly Care Research (NEUROTEC), Division of Molecular Neuropharmacology, Huddinge University Hospital, B84, S-141 86 Stockholm, Sweden.
Brain Res. 2002 Nov 29;956(2):358-66. doi: 10.1016/s0006-8993(02)03571-0.
Reductions in the number of neuronal nicotinic acetylcholine receptors (nAChRs) have been shown to occur in connection with Parkinson's disease (PD), but it is still unclear which subtype of this receptor is affected. In the present study we examined various nAChR subtypes employing ligand binding, as well as levels of subunit protein and mRNA in the brains of PD patients and age-matched controls. Binding of [3H]epibatidine and levels of alpha3 mRNA in the caudate nucleus and temporal cortex, but not in the hippocampus were significantly decreased in the PD brain. The level of the alpha3 protein subunit was significantly reduced in all these brain regions but there was no change in the level of alpha4. The level of the beta2 protein subunit in the temporal cortex and hippocampus and the beta2 mRNA in the temporal cortex was lowered. Both the levels of the alpha7 subunit protein and [125I]alpha-bungarotoxin binding were significantly increased in the temporal cortex of PD patients whereas the alpha7 mRNA level was unchanged. These findings reveal selective losses of the alpha3- and beta2-containing nAChRs and an increase in the alpha7 nAChRs that might be related to the pathogenesis of PD.
已证明与帕金森病（PD）相关的神经元烟碱型乙酰胆碱受体（nAChRs）数量会减少，但该受体的哪种亚型受到影响仍不清楚。在本研究中，我们采用配体结合以及PD患者和年龄匹配对照者大脑中各亚基蛋白和mRNA水平，检测了各种nAChR亚型。在PD大脑中，尾状核和颞叶皮质而非海马体中，[3H]埃博霉素的结合以及α3 mRNA水平显著降低。所有这些脑区中α3蛋白亚基水平显著降低，但α4水平无变化。颞叶皮质和海马体中β2蛋白亚基水平以及颞叶皮质中β2 mRNA水平降低。PD患者颞叶皮质中α7亚基蛋白水平和[125I]α - 银环蛇毒素结合均显著增加，而α7 mRNA水平未改变。这些发现揭示了含α3和β2的nAChRs的选择性丧失以及α7 nAChRs的增加，这可能与PD的发病机制有关。
