The loss of cholinergic neurons in the septal nucleus, diagonal band, and nucleus basalis has been implicated in the neuropathology of senile dimentia of the Alzheimer's type. Patients with this disorder exhibit profound memory and learning impairment and progressive intellectual deterioration. Experimental animals with lesions of the cholinergic septo-hippocampal pathway have also been shown to exhibit memory disorders. This behavioral deficit can be rectified with transplants containing cholinergic neurons from embryonic septal nucleus-diagonal band tissue. The recovery of behavioral function is associated with a transplant-derived reinnervation of the host brain along with a recovery of choline acetyltransferase activity, the enzyme involved in the synthesis of acetylcholine. The success of neural transplantation to the central nervous system has been confined primarily to the use of embryonic material as a source of donor tissue. Recently, new neuronal survival factors have been identified, and calcium free media have been developed that aid in the regeneration of axotomized neurons. We propose to investigate the use of these survival factors and media in conjunction with recently developed methods of dissociated cell suspensions to transplant adult neurons. Nerve cells in the septal nucleus-diagonal band region from adult rats will be dissociated in a calcium free regeneration-promoting media. The cell suspension will then be injected into the hippocampal formation of adult rats that have previously received lesions to denervate the intrinsic cholinergic fiber projections. After transplantation, parameters of fiber ingrowth as determined by acetylcholinesterase histochemistry and choline acetyltransferase activity will be assessed. These studies will provide information needed to assess the use of central cholinergic neurons from adult donors for transplantation. If such neurons are capable of innervating the hippocampus of the host brain, then they may eventually provide an invaluable source of tissue for transplantation to aid in the restoration of neural function lost through stroke, trauma, or progressive degenerative disorders.
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