INTRACEREBRAL INJECTION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 COAT PROTEIN GP120 DIFFERENTIALLY AFFECTS THE EXPRESSION OF NERVE GROWTH-FACTOR AND NITRIC-OXIDE SYNTHASE IN THE HIPPOCAMPUS OF RAT

We have studied the neuropathological characteristics of the brain of rats receiving daily intracerebroventricular administration of freshly dissolved human immunodeficiency virus type 1 recombinant protein gp1 20 (100 ng per rat per day) given for up to 14 days. Histological exam ination of serial brain sections revealed no apparent gross damage to the cortex or hippocampus, nor did cell counting yield significant neu ronal cell loss. However, the viral protein caused after 7 and 14 days of treatment DNA fragmentation in 10% of brain cortical neurons, Inte restingly, reduced neuronal nitric oxide synthase (NOS) expression alo ng with significant increases in nerve growth factor (NGF) were observ ed in the hippocampus, where gp120 did not cause neuronal damage. No c hanges in NGF and NOS expression were seen in the cortex, where cell d eath is likely to be of the apoptotic type. The present data demonstra te that gp120-induced cortical cell death is associated with the lack of increase of NGF in the cerebral cortex and suggest that the latter may be important for the expression of neuropathology in the rat brain . By contrast, enhanced levels of NGF may prevent or delay neuronal de ath in the hippocampus, where reduced NOS expression may be a reflecti on of a subcellular insult inflicted by the viral protein.