ALTERED CELL CALCIUM REGULATION IN SYNAPTOSOMES AND BRAIN-CELLS OF THE 30-MONTH-OLD RAT - PROMINENT EFFECTS IN HIPPOCAMPUS

A deficient regulation of neuronal cytosolic calcium levels has been s uggested to play a role in the pathogenesis of neurodegeneration. Howe ver, evidence for an alteration in cytosolic calcium regulation in old age is at present controversial. The present work was aimed at studyi ng whether changes in synaptosomal calcium homeostasis in 30-month-old rats are uniform throughout the brain or affect specific brain region s. A second question addressed in this work is whether the effect of a geing on calcium homeostasis is restricted to the nerve terminal or a more general process affecting also cell bodies. To study these questi ons cytosolic calcium regulation was studied in parallel in synaptosom es and a preparation of acutely dissociated brain cells obtained from different regions of 3- and 30-month-old rats. Ca-45(2+) accumulation and distribution in mitochondria (assessed as FCCP-releasable Ca-45(2)) was also studied. Mean [Ca2+](i) obtained at rest and after high K depolarization were unchanged in cerebral cortex synaptosomes but inc reased in hippocampal synaptosomes at 30 months. Resting [Ca2+](i) als o increased with age in hippocampal, but not cerebral cortex cells, wh ereas the increase in [Ca2+](i) obtained by depolarization was larger in both brain regions. Calcium compartmentation in mitochondria from h ippocampal neurons incubated under high K+ conditions was also decreas ed with ageing. An altered calcium regulation in cell bodies and synap tic terminals in the hippocampus may be involved in the development of functional impairments in the hippocampal formation.