Similar age-related changes of free intracellular calcium in lymphocytes and central neurons : effects of Alzheimer's disease

Several studies suggest that alterations of cytosolic free calcium concentration ([Ca2+]i) are involved in the pathophysiology of aging and Alzheimer's disease (AD). However, only few data are presently available giving detailed information about specific characteristics of age-related or AD-specific changes in cellular Ca(2+)-homeostasis. To allow a comprehensive evaluation of age-related changes in [Ca2+]i we performed parallel investigations in central mouse brain cells and mouse spleen lymphocytes of young and aged animals and also in human lymphocytes and granulocytes of young and aged donors and additionally of AD patients. In aged animals, basal [Ca2+]i was decreased in brain cells but increased in spleen lymphocytes. No age-related alterations in baseline [Ca2+]i was found in human lymphocytes or granulocytes. However, comparison of activation-induced rise in [Ca2+]i revealed parallel age-related changes in the different cell-types investigated. The increase in [Ca2+]i after depolarization of mouse brain cells with KCl and after stimulation of mouse lymphocytes with phytohaemagglutinin (PHA) was significantly impaired in aged animals. Moreover, activation of human lymphocytes with PHA also revealed a reduced increase in [Ca2+]i in cells of aged donors. In lymphocytes of AD-patients there was a tendency to higher basal [Ca2+]i compared to their aged matched controls, but no specific alterations in [Ca2+]i could be found after stimulation with PHA. Also no age-related or AD-specific changes were found in granulocytes after stimulation with N-formyl-methionyl-leucyl-phenylalanine (fMLP).(ABSTRACT TRUNCATED AT 250 WORDS)