Nerve growth factor (NGF) is a selective neurotrophic factor for basal forebrain cholinergic neurons a cell population affected in Alzheimer's disease (AD). It has been suggested that NGF may be useful in the treatment of the cholinergic abnormalities that occur in AD. As part of an effort to explore the therapeutic potential of NGF, we plan to develop an in vitro system to evaluate the effects of NGF on primate cholinergic neurons. Because of the complexity of nervous tissue in the intact animal and since direct access to measurements of NGF-induced biochemical events in targeted neuronal population is difficult, culture preparations of primate cells may help to evaluate this experimental therapy. The most readily available source of NGF is mouse salivary gland. Because of species differences, high concentrations of mouse NGF may be required to elicit neurite outgrowth from primate neurons. Therefore, we plan initially to evaluate the effects of various concentrations of mouse NGF on responses of dorsal root ganglia neurons obtained from fetal baboons. In addition, setal cholinergic neurons will be isolated from fetal baboons at various gestational stages and maintained in culture. The effect of NGF on the activity of choline acetyltransferase (ChAT) in these cells will measured to determine whether there is a developmental window for response in primates, as there is in rodents. Neurons obtained at the most sensitive fetal age will be used to establish NGF dose- response curves. The maximum response obtained in vitro may give some indication concerning the response to NGF that can be achieved in vivo.
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