title: Disturbances of the neuronal calcium homeostasis in the aging nervous system.
abstract: 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.
authors.affiliation: Central Institute of Mental Health, Dept. Psychopharmacology, Mannheim, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Hartmann
authors.forename: A
authors.initials: A
authors.lastname: Eckert
authors.forename: W E
authors.initials: WE
authors.lastname: Müller
mesh_terms: D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002118:Calcium