Studies in the past have suggested that hypertrophied astrocytes and nonastrocytes in the hippocampus of aged rats may be incapable of responding optimally to neural tissue damage. These studies have also supported the speculation that age-associated astrocyte hypertrophy and diminished glial efficacy may be attributed, at least in part, to elevated levels of circulating glucocorticoid hormones. The major objective of the proposed study is to test these two hypotheses. The first hypothesis will be tested by comparing reactive responses of hippocampal astrocytes in mature adult and mid-aged rats to determine whether or not astrocytes and nonastrocytes exhibit significant age-related decline in proliferation and lysosomal enzyme enhancement. The rate and magnitude of glial proliferation will be determined using quantitative 3H-thymidine autoradiography. The rate and magnitude of glial lysosomal enzyme increase will be evaluated by computer-assisted cytophotometric quantitation of acid phosphatase staining of astrocytes and nonastrocytes. The second hypothesis will be tested by determining whether or not the effects of aging on reactive capabilities of astrocytes and nonastrocytes may be reproduced in mature adult rats by elevation of the level of circulating corticoids through hormone administration. In addition, this part of the study will also establish the effectiveness of adrenalectomy of mature adult rats in preventing or reducing age-associated alterations in astrocyte and nonastrocyte reactivity. The results should elucidate age- related changes, if any, in reactive properties of astrocytes and nonastrocytes and provide clues on the role of corticoid hormones in modulating reactive properties of astrocytes and nonastrocytes during aging. Independent of its relevance to aging, the proposed study should provide clues on the possible perturbation of astrocyte and nonastrocyte functions in humans resulting from glucocorticoid therapy and/or conditions associated with high levels of corticoid hormones. By identifying cellular and subcellular properties of astrocytes and nonastrocytes which are subject to modulation in vivo, the results of the proposed study should also provide guidelines for the potential manipulation of astrocyte and nonastrocyte reactivity for facilitating optimal recovery of brain functions following neural tissue damage.
