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The Aging Brain
Symposium on The Aging Process
The Aging Brain Antonia Vernadakis, Ph.D.*
As also discussed throughout this book, the world's geriatric population is increasing at an alarming rate. Although many physiologic functions are known to deteriorate with advanced age, perhaps none are as tragic as those involving the central nervous system. Age-related neurologic dysfunctions and associated behavioral disturbances threaten the quality of life of the elderly and impose tremendous emotional and economic burdens on families and society. Ultimately, solutions to the neurologic problems of the elderly require a clearer understanding of the underlying neurologic mechanisms that become impaired and their relationship to the serious behavioral disturbances. Impairment of memory is known to occur in a large proportion of normal aged individuals, many studies having documented the difference between the young and old in the ability to learn new information . For many years it was believed that memory and cognitive decline of the aged was simply the result of attrition of nerve cells, which are estimated to be lost at the rate of 50,000 to 100,000 cells per day. However, although neuronal loss must play a role in the memory and cognitive decline of aging, it is now clear that this is not the complete explanation. The neuron is only one component of the complex circuitry of the brain. Another significant cellular component is the neuroglia cells, the satellite cells of the central nervous system (CNS). Additionally, connective tissue cells such as endothelial cells, fibroblasts, and mesenchymal cells constitute another significant cellular component of the brain cell circuitry. All these cell components-neurons, neuroglia, connective tissue-intercommunicate through their microenvironment and function as a unit (Fig. 1). Agerelated changes in any component of this cellular unit will shift the balance, interrupt intercellular relationships, and ultimately affect function .
*Professor, Departments of Psychiatry and Pharmacology, University of Colorado School of Medicine, Denver, Colorado
Clinics in Geriatric Medicine-Vol. 1, No. 1, February 1985
61
94
222. 223.
224. 225. 226.
227. 228. 229. 230. 231. 232. 233. 234.
ANTONIA VERNADAKIS H., and Parvez, S. (eds.): Neuroendocrinology of Hormone-Transmitter Interactions. Holland, V. N. U. International Sciences Press, 1985 (in press). Vernadakis, A., Mangoura, D., Sakellaridis, N., et al.: Glial cells dissociated from newborn and aged mouse brain. J. Neurosci. Res., 11:253-262, 1984. Vernadakis, A., Parker, K., Arnold, B. E., et al.: Role of glial cells in CNS aging. In Giacobini, E., Filogamo, G., Giacobini, G., et al. (eds.): The Aging Brain: Cellular and Molecular Mechanisms of Aging in the Nervous System. New York, Raven Press, 1982, pp. 57-68. Vijayashankar, N., and Brody, H.: A study of aging in the human abducens nucleus. J. Comp. Neural., 173:433-438, 1977. Vijayashankar, N. , and Brody, H.: Aging in the human brain stem: A study of the nucleus of the trachlear nerve. Acta Anat. , 99:169-172, 1977. Vijayashankar, N., and Brody, H.: A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging. J. Neuropathol. Exp. Neural., 38:490-497, 1979. Virchow, R.: Uber das granulinte ansehan det wunderungen des gehirn-rentrikal. Allerg. Zschr. Psychiatr., 3:424-450, 1846. Ward, D. G., Grizzle, W., and Gann, D.: Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in cat. Endocrinology, 99:1220-1228, 1976. Weiskrantz, L., and Warrington, E.: A study of forgetting in amnesic patients. Neuropsychologia, 8:281-288, 1970. Wheeler, D. D. : Aging of membrane transport mechanisms in the central nervous system: High affinity glutamic acid transport in rat cortical synaptosomes. Exp. Gerontol. , 15:269-284, 1980. Wheeler, D. D.: Aging of membrane transport mechanisms in the central nervous system: GABA transport in rat cortical synaptosomes. Exp. Gerontol., 17:71-85, 1982. Wheeler, D. D.: Aging of the high affinity GABA transporter in synaptosomes from the hypothalamus of the rat. Exp. Gerontol., 18:125--135, 1983. White, P., Hiley, C. R., Goodhardt, M. J., et al.: Neocortical cholinergic neurons in elderly people. Lancet, 1:668-671, 1977. Whitehouse, P. J., Price, D. L., Struble, R. G., et al.: Alzheimer's disease and senile dementia: Loss of neurons in the basal forebrain . Science, 215:1237- 1239, 1982.
235. Wiklund, L. , and Bjorklund, A.: Mechanisms of regrowth in the bulbospinal serotonin system following 5,6-dihydroxytyptamine induced anatomy. II. Fluorescence histochemical observations. Brain Res., 191:129-160, 1980. 236. Wilkinson, A. , and Davies, I.: The influence of age and dementia on the neuron population of the mammillary bodies. Age Ageing, 7:151-160, 1978. 237. Wisniewski, H. M., and Igbal, K.: Ageing of the brain and dementia. Trends Neurosci. , 3:226-228, 1980. 238. Wisniewski, H. M., Narang, H. K., and Terry, R. D.: Neurofibrillary tangles of paired helical filaments. J. Neurol. Sci., 7:173-181, 1976. 239. Wree, A., Braak, H., Schleicher, A., et al.: Biomathematical analysis of the neuronal loss in the aging brain of both sexes, demonstrated in pigment preparations of the para cerebellaris locus coerulei. Anat. Embryo!. , 160:105--119, 1980. 240. Yamada, M.: Zahlemassige verterlung der dendritendorne am zpikalen dedriten der pyramidenzellen bein morbus and seniler demez. Bull. Yamaguchi Med. Sch., 23:229235, 1976. 241. Zornetzer, S. F ., Abraham, W., and Appleton, R.: The locus coeruleus and labile memory. Pharmacol. Biochem. Behav. , 9:227- 234, 1978. Departments of Psychiatry and Pharmacology School of Medicine University of Colorado 4200 East Ninth Avenue Denver, Colorado 80262
The Aging Brain Antonia Vernadakis, Ph.D.*
As also discussed throughout this book, the world's geriatric population is increasing at an alarming rate. Although many physiologic functions are known to deteriorate with advanced age, perhaps none are as tragic as those involving the central nervous system. Age-related neurologic dysfunctions and associated behavioral disturbances threaten the quality of life of the elderly and impose tremendous emotional and economic burdens on families and society. Ultimately, solutions to the neurologic problems of the elderly require a clearer understanding of the underlying neurologic mechanisms that become impaired and their relationship to the serious behavioral disturbances. Impairment of memory is known to occur in a large proportion of normal aged individuals, many studies having documented the difference between the young and old in the ability to learn new information . For many years it was believed that memory and cognitive decline of the aged was simply the result of attrition of nerve cells, which are estimated to be lost at the rate of 50,000 to 100,000 cells per day. However, although neuronal loss must play a role in the memory and cognitive decline of aging, it is now clear that this is not the complete explanation. The neuron is only one component of the complex circuitry of the brain. Another significant cellular component is the neuroglia cells, the satellite cells of the central nervous system (CNS). Additionally, connective tissue cells such as endothelial cells, fibroblasts, and mesenchymal cells constitute another significant cellular component of the brain cell circuitry. All these cell components-neurons, neuroglia, connective tissue-intercommunicate through their microenvironment and function as a unit (Fig. 1). Agerelated changes in any component of this cellular unit will shift the balance, interrupt intercellular relationships, and ultimately affect function .
*Professor, Departments of Psychiatry and Pharmacology, University of Colorado School of Medicine, Denver, Colorado
Clinics in Geriatric Medicine-Vol. 1, No. 1, February 1985
61
94
222. 223.
224. 225. 226.
227. 228. 229. 230. 231. 232. 233. 234.
ANTONIA VERNADAKIS H., and Parvez, S. (eds.): Neuroendocrinology of Hormone-Transmitter Interactions. Holland, V. N. U. International Sciences Press, 1985 (in press). Vernadakis, A., Mangoura, D., Sakellaridis, N., et al.: Glial cells dissociated from newborn and aged mouse brain. J. Neurosci. Res., 11:253-262, 1984. Vernadakis, A., Parker, K., Arnold, B. E., et al.: Role of glial cells in CNS aging. In Giacobini, E., Filogamo, G., Giacobini, G., et al. (eds.): The Aging Brain: Cellular and Molecular Mechanisms of Aging in the Nervous System. New York, Raven Press, 1982, pp. 57-68. Vijayashankar, N., and Brody, H.: A study of aging in the human abducens nucleus. J. Comp. Neural., 173:433-438, 1977. Vijayashankar, N. , and Brody, H.: Aging in the human brain stem: A study of the nucleus of the trachlear nerve. Acta Anat. , 99:169-172, 1977. Vijayashankar, N., and Brody, H.: A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging. J. Neuropathol. Exp. Neural., 38:490-497, 1979. Virchow, R.: Uber das granulinte ansehan det wunderungen des gehirn-rentrikal. Allerg. Zschr. Psychiatr., 3:424-450, 1846. Ward, D. G., Grizzle, W., and Gann, D.: Inhibitory and facilitatory areas of the rostral pons mediating ACTH release in cat. Endocrinology, 99:1220-1228, 1976. Weiskrantz, L., and Warrington, E.: A study of forgetting in amnesic patients. Neuropsychologia, 8:281-288, 1970. Wheeler, D. D. : Aging of membrane transport mechanisms in the central nervous system: High affinity glutamic acid transport in rat cortical synaptosomes. Exp. Gerontol. , 15:269-284, 1980. Wheeler, D. D.: Aging of membrane transport mechanisms in the central nervous system: GABA transport in rat cortical synaptosomes. Exp. Gerontol., 17:71-85, 1982. Wheeler, D. D.: Aging of the high affinity GABA transporter in synaptosomes from the hypothalamus of the rat. Exp. Gerontol., 18:125--135, 1983. White, P., Hiley, C. R., Goodhardt, M. J., et al.: Neocortical cholinergic neurons in elderly people. Lancet, 1:668-671, 1977. Whitehouse, P. J., Price, D. L., Struble, R. G., et al.: Alzheimer's disease and senile dementia: Loss of neurons in the basal forebrain . Science, 215:1237- 1239, 1982.
235. Wiklund, L. , and Bjorklund, A.: Mechanisms of regrowth in the bulbospinal serotonin system following 5,6-dihydroxytyptamine induced anatomy. II. Fluorescence histochemical observations. Brain Res., 191:129-160, 1980. 236. Wilkinson, A. , and Davies, I.: The influence of age and dementia on the neuron population of the mammillary bodies. Age Ageing, 7:151-160, 1978. 237. Wisniewski, H. M., and Igbal, K.: Ageing of the brain and dementia. Trends Neurosci. , 3:226-228, 1980. 238. Wisniewski, H. M., Narang, H. K., and Terry, R. D.: Neurofibrillary tangles of paired helical filaments. J. Neurol. Sci., 7:173-181, 1976. 239. Wree, A., Braak, H., Schleicher, A., et al.: Biomathematical analysis of the neuronal loss in the aging brain of both sexes, demonstrated in pigment preparations of the para cerebellaris locus coerulei. Anat. Embryo!. , 160:105--119, 1980. 240. Yamada, M.: Zahlemassige verterlung der dendritendorne am zpikalen dedriten der pyramidenzellen bein morbus and seniler demez. Bull. Yamaguchi Med. Sch., 23:229235, 1976. 241. Zornetzer, S. F ., Abraham, W., and Appleton, R.: The locus coeruleus and labile memory. Pharmacol. Biochem. Behav. , 9:227- 234, 1978. Departments of Psychiatry and Pharmacology School of Medicine University of Colorado 4200 East Ninth Avenue Denver, Colorado 80262