Hartmann H, Eckert A, Müller W E
Central Institute of Mental Health, Dept. Psychopharmacology, Mannheim, Germany.
Life Sci. 1994;55(25-26):2011-8. doi: 10.1016/0024-3205(94)00381-5.
Maintenance of the cellular calcium homeostasis plays an important role for neuronal cell function and interneuronal cell to cell communication. Therefore, alterations of the neuronal Ca2+ homeostasis may play a crucial role for brain aging in general and for age-related deficits in cognitive functions particularly. Numerous studies indicate various disturbances of the Ca2+ homeostasis on different levels like Ca2+ channel properties, 45Ca2+ uptake, or Ca2+ binding proteins. Investigations on alterations of the free intracellular calcium concentration ([Ca2+]i) in presynaptic synaptosomal preparations led to inconsistent results reporting increased or unchanged [Ca2+]i in aged animals. Postsynaptic alterations of [Ca2+]i have been investigated mainly indirectly by electrophysiological methods and revealed prolonged Ca(2+)-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the first time to evaluate age-dependent alterations of postsynaptic [Ca2+]i directly. In neurons of aged mice basal [Ca2+]i was reduced and depolarization-induced rise in [Ca2+]i was also reduced, probably as a result of increased activation of Ca(2+)-dependent mechanisms terminating Ca(2+)-influx. Depolarization-induced, Ca(2+)-mediated inositolphosphate accumulation was also increased in aged animals. This leads to the conclusion that Ca(2+)-dependent intracellular processes become more sensitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consistent destabilizating effect of this peptide on K(+)-induced rise in [Ca2+]i which may result in chronically increased neuronal vulnerability. Together with increased Ca2+ sensitivity during aging this might be one of the reasons for the increasing prevalence of Alzheimer's disease (AD) with aging.
维持细胞钙稳态对神经元细胞功能以及神经元间的细胞通讯起着重要作用。因此，神经元钙稳态的改变可能在一般脑老化过程中，尤其是在与年龄相关的认知功能缺陷中起关键作用。大量研究表明，在不同水平上存在各种钙稳态紊乱，如钙通道特性、45Ca2+摄取或钙结合蛋白。对突触前突触体制剂中细胞内游离钙浓度（[Ca2+]i）变化的研究结果不一致，有的报告老年动物的[Ca2+]i升高，有的则报告不变。突触后[Ca2+]i的变化主要通过电生理方法间接研究，结果显示钙依赖性超极化后电位延长或钙峰持续时间延长。通过使用急性解离的小鼠脑细胞，首次能够直接评估突触后[Ca2+]i的年龄依赖性变化。在老年小鼠的神经元中，基础[Ca2+]i降低，去极化诱导的[Ca2+]i升高也降低，这可能是由于终止钙内流的钙依赖性机制激活增加所致。老年动物去极化诱导的、钙介导的肌醇磷酸积累也增加。这导致得出结论，钙依赖性细胞内过程在衰老过程中变得更加敏感。在同一系统中关于β-淀粉样蛋白对钙稳态影响的研究表明，该肽对钾诱导的[Ca2+]i升高有小但一致的不稳定作用，这可能导致神经元长期易损性增加。随着衰老过程中钙敏感性增加，这可能是阿尔茨海默病（AD）患病率随年龄增长而增加的原因之一。
