Age-related deficits in central transmitters have been discovered for several neural systems. Some groups of monoaminergic and peptidergic neurons appear to show this decline in both rodent and primate brain. Numerous human neurodegenerative disorders are characterized by similar declines in transmitters. The aged brain recently has been shown to possess a marked plasticity as measured, for example, by growth of dendrites in cortex and by growth of catecholamine fibers from the medial forebrain bundle following surgical intervention. This plasticity suggests that neural reorganization may occur during aging and further, that the aged brain may be receptive in an integrative sense, to neural transplants. Neural transplantation techniques have been shown to reverse or improve some genetic or degenerative deficits in brain function in young animals and, in one instance, in aged rats. The present proposal is designed to test the potential of neural grafts to improve lost or diminished brain function associated with vasopressin neurons of the supraoptic nucleus and noradrenergic neurons of the locus coeruleus, using a combination of endocrine, behavioral, neurochemical and morphological measures in rodent and then to extend this question to non-human primate in order to determine optimal grafting conditions in young and aged macaques as a prerequisite for potential clinical tests.
