DISTURBANCES OF THE NEURONAL CALCIUM HOMEOSTASIS IN THE AGING NERVOUS-SYSTEM

Maintenance of the cellular calcium homeostasis plays an important rol e for neuronal cell function and interneuronal cell to cell communicat ion. 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 variou s disturbances of the Ca2+ homeostasis on different levels like Ca2+ c hannel properties, Ca-45(2+) uptake, or Ca2+ binding proteins. Investi gations on alterations of the free intracellular calcium concentration ([Ca2+](i)) in presynaptic synaptosomal preparations led to inconsist ent 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 Ca2-dependent afterhyperpolarization or prolonged Ca2+ spike duration. By using acutely dissociated mouse brain cells it was possible for the f irst 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 Ca2+-dependent mechanisms termina ting Ca2+-influx. Depolarization-induced, Ca2+-mediated inositolphosph ate accumulation was also increased in aged animals. This leads to the conclusion that Ca2+-dependent intracellular processes become more se nsitive during aging. Investigations about the effect of beta-amyloid on the Ca2+ homeostasis in the same system revealed a small but consis tent 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 diseas e (AD) with aging.