AGE-RELATED-CHANGES IN CALCIUM HOMEOSTATIC MECHANISMS IN SYNAPTOSOMESIN RELATION WITH WORKING-MEMORY DEFICIENCY

Aging is associated with alterations in different systems that govern neuronal calcium homeostasis. This study was designed to determine whe ther any of these alterations may contribute to the decline in spatial working memory that is observed in old rats. Several parameters [init ial (5 s) and steady state (15 min) Ca-45(2+) uptake, FCCP-releaseable Ca-45(2+), [Ca2+]i levels, depolarization-induced phosphoprotein (P97 , PP65, P42) dephosphorylation and acetylcholine levels and release) i nvolved in calcium homeostasis/signaling were determined in whole brai n synaptosomes derived from adult (9-month-old) and old (24-month-old) rats that were evaluated for spatial memory performance in the eight- arm radial maze. The neurochemical analysis indicated that both the 9- and 24-month-old rats were impaired with respect to 3-month-old anima ls. When learners (animals reaching criterion; RC) were compared to me mory impaired rats (MI), it was found that the FCCP-releaseable Ca-45( 2+) of Synaptosomes, that reflects mitochondrial calcium, was lower in the MI than the RC rats and was correlated with the behavioral perfor mance of the rats in their first testing sessions. The results suggest that the loss of calcium uptake capacity in synaptic mitochondria dur ing aging may be associated with impaired working memory in old animal s.