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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.

journal_name

Life Sci

journal_title

Life sciences

authors

Hartmann H,Eckert A,Müller WE

doi

10.1016/0024-3205(94)00381-5

subject

Has Abstract

pub_date

1994-01-01 00:00:00

pages

2011-8

issue

25-26

eissn

0024-3205

issn

1879-0631

pii

0024-3205(94)00381-5

journal_volume

pub_type

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Disturbances of the neuronal calcium homeostasis in the aging nervous system.