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

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Abstract
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 Ca2+-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-fomyl-methionyl-leucyl-phenylalanine (fMLP). Since K+- and PHA-induced rise in [Ca2+]i is mainly mediated by Ca2+-influx, whereas fMLP-stimulated rise in [Ca2+]i is mainly due to intracellular Ca2+-release, our findings might indicate that age-related disturbances of Ca2+-homeostasis especially affect mechanisms involved in Ca2+-influx. The corresponding age-related alterations in mouse brain cells, mouse spleen lymphocytes and human lymphocytes after cell activation suggest a similar impairment of Ca2+-homeostatis in these cells and might justify the speculation that Ca2+-homeostasis in the aged human brain is affected in a comparable fashion.