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Functional compensation afforded by grafts of foetal neurones
1Merck Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Marlow, Essex, U.K.
Abstract:
1. Adult neurones grafted to the adult nervous system show limited survival and growth potential. By contrast, certain foetal neurones of a defined age, when grafted to the damaged adult nervous system survive, and form a dense innervation of the host brain with morphologically defined synapses. Monamine containing neurones in the rat have these properties. In a number of model systems their ability to survive grafting to the adult brain has been demonstrated, the optimal conditions for their survival and the importance of endogenous growth factors continue to be investigated. 2. Lesions of the ascending dopamine pathways to the dorsal and ventral striatum result in profound motor disorders. Dopamine-rich foetal neurones from the mesencephalon grafted as blocks of tissue or as cell suspensions provide a rich innervation to the dopamine-depleted target areas and reverse many of these motor impairments. Similar models have been developed for the cholinergic innervation from the basal forebrain to the hippocampus and cortex. Cholinergic depletion of these forebrain structures impair performance on spatial memory tasks, which are reversed by grafts of foetal basal forebrain neurones to cortex or hippocampus. 3. The grafting model is a powerful tool with which to define the functional role of neurotransmitters in brain function. The neurological properties of foetal monoamine and cholinergic neurones which underlie their ability to afford functional compensation to the damaged nervous system and their vulnerability in certain degenerative diseases of the CNS in man remain obscure.