Calcium homeostasis and modulation of synaptic plasticity in the aged brain.
The level of intracellular Ca2+ plays a central role in normal and pathological signaling within and between neurons. These processes involve a cascade of events for locally raising and lowering cytosolic Ca2+. As the mechanisms for age-related alteration in Ca2+ dysregulation have been illuminated, hypotheses concerning Ca2+ homeostasis and brain aging have been modified. The idea that senescence is due to pervasive cell loss associated with elevated resting Ca2+ has been replaced by concepts concerning changes in local Ca2+ levels associated with neural activity. This article reviews evidence for a shift in the sources of intracellular Ca2+ characterized by a diminished role for N-methyl-D-aspartate receptors and an increased role for intracellular stores and voltage-dependent Ca2+ channels. Physiological and biological models are outlined, which relate a shift in Ca2+ regulation with changes in cell excitability and synaptic plasticity, resulting in a functional lesion of the hippocampus.
Foster
Thomas C
TC
Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. foster@mbi.ufl.edu
D000368:Aged; D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D008954:Models, Biological; D019636:Neurodegenerative Diseases / Q000235:genetics* / Q000378:metabolism; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress; D015398:Signal Transduction; D013569:Synapses / Q000502:physiology*
D015220:Calcium Channels; D002118:Calcium