Neurotransmitter Receptor Changes in the Hippocampus and Cerebral Cortex in Normal Aging
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).
KeywordsDementia Nicotine Neurol NMDA Choline
Unable to display preview. Download preview PDF.
- Biggio, G., and Costa, E., 1988, Chloride channels and their modulation by neurotransmitters and drugs, in: Advances in Biochemical Psychopharmacology, Vol. 45, Raven, New York.Google Scholar
- Geinisman, Y., DeToledo-Morrell, L., Morrell, F., Persina, I. S., and Rossi, M., 1992, Age-related loss of axospinous synapses formed by two afferent systems in the rat dentate gyrus as revealed by the unbiased sterological dissector technique, Hippocampus 2:432–444.Google Scholar
- Keen, M., and MacDermot, J., 1993, Analysis of receptors by radioligand binding, in: Receptor Autoradiography Principles and Practice, (J. Wharton and J. M. Polak, eds.), Oxford University Press, London, pp. 23–55.Google Scholar
- Kemper, T. L., 1994, Neuroanatomical and neuropathological changes during aging and dementia, in: Clinical Neurology and Aging (M. L. Albert and J. E. Knoefel, eds.), Oxford University Press, New York, pp. 3–67.Google Scholar
- Monaghan, D. T., Nguyen, L., and Cotman, C. W., 1986, The distribution of [3H]kainate binding sites in primate hippocampus is similar to the distribution of both Ca2+-sensitive and Ca2 +-insensitive [3H]kainate binding sites in rat hippocampus, Neurochem. Res. 11:1073–1082.PubMedCrossRefGoogle Scholar
- Subramaniam, S., and McGonigle, P., 1991, Quantitative autoradiographic characterization of the binding of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) in rat brain: Regional effects of polyamines, J. Pharm. Exp. then 256:811–819.Google Scholar
- Wagster, M. V., Whitehouse, P. J., Walker, L. C., Kellar, K. J., and Price, D. L., 1990, Laminar organization of age-related loss of cholinergic receptors in temporal neocortex of rhesus monkey, J. Neurosci. 51:2879–2885.Google Scholar
- Wallace, D. C., 1995, Mitochondrial DNA mutations, in: Human Disease and Aging: Molecular Aspects of Aging (K. Esser and G. M. Martin, eds.), Wiley, New York, pp. 163–177.Google Scholar