HIV-1 GP120 PRODUCES DNA FRAGMENTATION IN THE CEREBRAL-CORTEX OF RAT

In the present experiments we have used morphological techniques to study the neuropathological pro file of the brain of rats after intracerebroventricular (i.c.v.) injection of recombinant HIV-1 gp 120. Using brain cryostat sections (10 mu m) from rats treated with a single, daily dose of gp120 (100 ng/rat) given for 7 and 14 consecutive days, in situ DNA fragmentation was revealed in the neocortex but not in the hippocampus by terminal deoxylnucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labelling (TUNEL). In these rats, dark degenerating neurones were observed in the neocortex but not in the hippocampus. Treatment with bovine serum albumin (300 ng/rat i.c.v.) for up to 14 days did not produce DNA fragmentation nor did it yield neuropathological lesions of the neocortex or hippocampus. In conclusion the present data demonstrate that gp 120 given i.c.v. produced DNA fragmentation in the neocortex, thus suggesting that apoptosis is the mechanism through which neurones ones of the neocortex are killed. (C) 1995 Academic Press, Inc.