Rogers S W, Gahring L C, Collins A C, Marks M
Salt Lake City Veterans Affairs Medical Center, Geriatric Research, Education, and Clinical Center, and the University of Utah School of Medicine, Salt Lake City, Utah 84112, USA.
J Neurosci. 1998 Jul 1;18(13):4825-32. doi: 10.1523/JNEUROSCI.18-13-04825.1998.
The distribution of the neuronal nicotinic acetylcholine receptor subunit alpha4 (nAChRalpha4) in the brains of young (2-4 months) or aged (24-28 months) CBA/J mice was examined using immunohistochemical staining. Anti-nAChRalpha4 immunoreactivity corresponded with nAChRalpha4 RNA expression and high-affinity [3H]nicotine binding. Immunostaining in aged mice relative to that in young animals was diminished in the medial septum and diagonal band but was unchanged in the globus pallidus and substantia nigra. The staining of neurons was almost completely absent in the hippocampus of aged animals. The oral administration of nicotine to aged animals for 6 weeks did not alter nAChRalpha4 expression relative to that in aged controls. However, the long-term delivery of nicotine (11 months) to 14-month-old animals corresponded with the highly specific preservation of nAChRalpha4 expression in some neurons of the dentate gyrus region and in neurite processes of remaining neurons of the hippocampal CA1 region. These results support the conclusion that the loss of nAChRalpha4 expression occurs in key cholinergic regions during normal aging. Furthermore, sustained long-term nicotine delivery may promote highly region-specific retention of nAChR expression, but only if initiated before normal age-related receptor decline.
采用免疫组织化学染色法，检测了年轻（2 - 4个月）和老年（24 - 28个月）CBA/J小鼠大脑中神经元烟碱型乙酰胆碱受体α4亚基（nAChRα4）的分布情况。抗nAChRα4免疫反应性与nAChRα4 RNA表达及高亲和力[³H]尼古丁结合情况相符。与年轻动物相比，老年小鼠内侧隔区和斜角带的免疫染色减弱，但苍白球和黑质的免疫染色没有变化。老年动物海马体中几乎完全没有神经元染色。对老年动物口服尼古丁6周，相对于老年对照组，nAChRα4表达没有改变。然而，对14个月大的动物长期给予尼古丁（11个月），与齿状回区域的一些神经元以及海马CA1区域其余神经元的神经突中nAChRα4表达的高度特异性保留有关。这些结果支持以下结论：在正常衰老过程中，nAChRα4表达在关键胆碱能区域丢失。此外，持续长期给予尼古丁可能促进nAChR表达的高度区域特异性保留，但前提是在正常年龄相关受体下降之前开始给药。
