ABSTRACT
The first element of Z. S. Khachaturian’s construct was simply that the cellular mechanisms that participate in Ca2+ homeostasis play an important role in the process of aging and neurodegeneration. The morphological changes in Alzheimer’s disease, such as dendritic pruning and loss of synapses and neurons, involve the same mechanisms that are responsible for neuroplasticity in the developing or mature brain. The term “excitotoxicity” was first coined by J. W. Olney in 1970 to describe the excessive activation of glutamate receptors that follows neuronal deprivation of oxygen and/or nutrients and resulting in neuronal death. The lack of significant effect of aging on AMPA binding is consistent with the electrophysiological studies of the AMPA response showing no age-related changes in either the mean quantal sizes or the unitary synaptic response. The age-dependent changes in the activity of various Ca2+ entry systems illustrate the problems in interpretation.
