DOWN-REGULATION OF FREE INTRACELLULAR CALCIUM IN DISSOCIATED BRAIN-CELLS OF AGED MICE AND RATS

Age-related changes in resting levels of the free intracellular calciu m concentration ([Ca2+](i)) as well as alterations of the rise in [Ca2 +](i) following depolarization have been investigated in acutely isola ted cells of the mouse brain and of various regions of the rat brain. Resting [Ca2+](i) as well as Ca2+ responses after depolarization were lower in brain cells of aged mice and in hippocampus and cortex cells, but not striatum or cerebellum cells of aged rats. It is concluded th at the Ca2+ homeostasis is specially susceptible to the aging process in some brain regions only, resulting in a down regulation of [Ca2+](i ) probably as a consequence of an enhanced sensitivity of mechanisms r egulating [Ca2+](i). This speculation was confirmed by an enhanced sen sitivity of Ca2+-stimulated phospholipase C activity in the aging mous e brain. The alterations of the central Ca2+ homeostasis in the mouse and the rat were paralleled by comparable changes of [Ca2+](i) in sple enocytes of both species in aging. The rise of [Ca2+](i) after stimula tion with the mitogen phytohemagglutinin (PHA) was significantly reduc ed in the plateau phase, which is maintained by Ca2+ influx mechanisms . Moreover, a reduced Ca2+ response was also found after stimulation o f the cells with the Ca2+ ionophore A23187. The data may indicate that comparable disturbances of the Ca2+ homeostasis occur in central and peripheral cells and that these alterations mainly affect transmembran eous Ca2+ fluxes rather than Ca2+ release from intracellular stores. T hese alterations may be compensated under normal conditions. However, in situations of additional stress like ischemia or hypoglycemia, the preexisting alterations of Ca2+ homeostasis may result in a reduced ca pacity for adaptation. This assumption was supported by observations i ndicating that the down-regulation of [Ca2+](i) after subchronic treat ment with nimodipine (20 mg/kg, 14 days) was less in brain cells of ag ed than of young mice.