PERSISTENT TRANSGENE EXPRESSION IN THE HYPOTHALAMUS FOLLOWING STEREOTAXIC DELIVERY OF A RECOMBINANT ADENOVIRUS - SUPPRESSION OF THE IMMUNE-RESPONSE WITH CYCLOSPORINE

Replication deficient, recombinant adenoviruses (Ads) have been used s uccessfully to transfect several forebrain and brainstem nuclei, but h ave yet to be demonstrated as useful vectors for transgene delivery in the structurally diverse and highly vascularised nuclei of the hypoth alamus. In the present study we have assessed the ability of an Ad exp ressing the lac-Z gene to transfect cells of the paraventricular nucle us (PVN) of the hypothalamus in vivo. We show that: (1) we can achieve stable expression of the lacZ gene in cells of the magnocellular PVN for at least 2 months; (2) there were no obvious differences in the le vel of AVP mRNA in the PVNs injected with Ad compared with those injec ted with vehicle suggesting that Ad treatment is not disrupting normal cellular function in the injection region (3) the introduction of Ads results in a limited immune response ; (4) systemic treatment with cy closporin dramatically reduces its magnitude. We conclude that Ad vect ors represent useful tools for neuroendocrinological and gene therapeu tic studies of the hypothalamus.