IN-UTERO GENE-TRANSFER REVEALS SURVIVAL EFFECTS OF NERVE GROWTH-FACTOR ON RAT-BRAIN CHOLINERGIC NEURONS DURING DEVELOPMENT

Nerve growth factor (NGF) is a maintenance factor for cholinergic neur ones in the brain, but its properties as a developmental survival fact or are largely unknown. The low accessibility of the developing mammal ian brain to experimental manipulation makes it difficult to increase NGF levels during the early phases of brain development. In the presen t study we have used an in utero, ex-vivo gene transfer approach to ex plore NGF actions during development of the cholinergic system in the rat brain. Significantly increased numbers of cholinergic neurones wer e found only in the mesopontine complex in animals receiving NGF-secre ting transplants, whereas the cholinergic neurones in the basal forebr ain and striatum were not clearly affected. The present results sugges t that overexpression of NGF during development may promote the surviv al of distinct populations of central cholinergic neurones into adulth ood.