Free intracellular calcium in aging and Alzheimer's disease.
Brain cells of aged mice exhibit distinct alterations of [Ca2+]i regulation resulting in lower levels of [Ca2+]i after stimulation. These alterations are probably more related to disturbances of mechanisms regulating transmembraneous Ca2+ fluxes than to mechanisms of intracellular Ca2+ release and storage. Comparable although not identical disturbances of [Ca2+]i regulation are present in mouse, rat, and human lymphocytes. Accordingly, one is tempted to speculate that in the human brain similar alterations of [Ca2+]i regulation might be present in aging as found in the aged mouse and rat brain. Since the downregulation of [Ca2+]i levels in aged brain cells seems to be accompanied by an enhanced intracellular sensitivity for changes of [Ca2+]i, both divergent alterations might compensate each other under normal conditions. However, it seems quite conceivable that the ability of the Ca2+ signal transduction pathway to adopt to periods of over-or understimulation (e.g., hypoxia, stress) might be disturbed in the aging brain. One of those conditions of additional alterations of [Ca2+]i regulation might be AD. Although we did not see AD-specific changes of [Ca2+]i regulation per se, the effect of beta A4 on cellular [Ca2+]i regulation was significantly and specifically disturbed in AD. It is not unlikely that a small, but long lasting (years or even decades) alterations of cellular [Ca2+]i regulation by beta A4, which is a product of normal brain metabolism, might finally contribute to the severe neuronal damage seen during the disease.
Müller
W E
WE
Department of Psychopharmacology, Central Institute of Mental Health Mannheim, Germany.
Hartmann
H
H
Eckert
A
A
Velbinger
K
K
Förstl
H
H
D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011188:Potassium / Q000494:pharmacology; D051381:Rats
D011188:Potassium; D002118:Calcium