Neurotransmitter Receptor Changes in the Hippocampus and Cerebral Cortex in Normal Aging

Abstract

As humans grow older, they all experience changes in their basic physiological systems. Although some of these changes can be debilitating or fatal, the quality of life during aging depends to a great extent on the functional status of the central nervous system. Over the past three decades, increasingly well-controlled and well-documented studies in humans and experimental animals have shown a variety of cognitive changes, including impairments in both memory and executive system function. In contrast to age-related dementias like Alzheimer’s disease, these impairments are relatively mild, though they increase in severity with age and can become quite troublesome (see Moss and Albert, this volume). It seems likely that these changes in cognitive function result from changes localized in the cerebral cortex (including the hippocampal formation and other parts of the limbic system) or related parts of the forebrain (thalamus, basal ganglia, amygdala, basal fore-brain). Investigations of the forebrain in both aged humans and experimental animals have uncovered a variety of age-related biological changes, including the appearance of amyloid plaques (e.g. Selkoe et al., 1987), loss of neurons (e.g. Brody, 1955; Brizzee et al., 1980), loss of myelin (e.g., Kemper, 1994), loss of synapses (e.g. Geinisman et al., 1992), decreases in neurotransmitter levels (e.g. Wenk et al., 1989), loss of neurotransmitter receptors (e.g. Wagster et al., 1990), alterations in mitochondrial energy metabolism (e.g. Wallace, 1995), and changes in neuro-physiological responsivity (e.g. Barnes, 1994; Tanila et al., 1997).