DIRECT INTRACEREBRAL NERVE GROWTH-FACTOR GENE-TRANSFER USING A RECOMBINANT ADENOVIRUS - EFFECT ON BASAL FOREBRAIN CHOLINERGIC NEURONS DURING AGING

Gene therapy in the nervous system offers an attractive strategy for t he administration of therapeutic factors in a potentially region-speci fic, sustained, and well-tolerated manner. We tested the trophic effec t of a recombinant adenovirus encoding nerve growth factor (AdNGF) in vivo on basal forebrain cholinergic neurons of aged rats, a neuronal p opulation affected during normal and pathological aging. Three weeks a fter unilateral injection of the recombinant adenovirus into the nucle us basalis magnocellularis, a significant increase in the somal areas of cholinergic neurons ipsilateral to the injection was observed. No i ncrease was detected in animals receiving a recombinant adenovirus car rying the Escherichia coil Lac Z reporter gene. Injected animals did n ot lose weight, an adverse effect usually described after intracerebro ventricular infusion of NGF, and no tissue loss or massive local infla mmatory response was observed around injection sites. Thus, a single i ntracerebral injection of AdNGF produces trophic effects similar to th ose resulting from chronic intracerebroventricular high levels of NGF. These findings indicate that recombinant adenoviruses encoding growth factors are potentially powerful tools for improving neuronal deficit s associated with degenerative processes. (C) 1996 Academic Press, Inc .