PEPTIDE-T PREVENTS NBM LESION-INDUCED CORTICAL ATROPHY IN AGED RATS

Because VIP is known to be neurotrophic in vitro, the present study te sted whether peptide T (PT), an octapeptide with a pentapeptide sequen ce homologous to VIP, could prevent nucleus basalis (NBM)-induced dege nerative changes in the parietal neocortex of aged rats. Aged (20-21 m onths old) Sprague-Dawley rats were given bilateral neurotoxic lesions of the NBM, and injected daily with PT (1 mg, IP) or vehicle solution for 5 months. Compared to unoperated controls, vehicle-treated NBM le sioned animals had: 1) a significant 17% decrease in overall cortical thickness, 2) significant decreases of 13-29% in the thickness of cort ical layers II-IV, V, and VI, and 3) significant neuronal and glial ce ll loss in layer V. PT treatment prevented or attenuated these lesion- induced decreases in cortical thickness and attenuated the accompanyin g loss of large neurons in layer V. These results provide evidence tha t PT, perhaps acting via VIP receptor stimulation, is neurotrophic and important for the integrity of brain tissue following denervation.