Effects of wheatgerm agglutinin and aging on the regional brain uptake of HIV-1GP120

HIV-1 is associated with infection and altered functions of the CNS, especi ally in the elderly. Most studies indicate that HIV-1 is not evenly distrib uted throughout the CNS but is concentrated in deep brain nuclei. This stud y examined whether regional or age-related differences in the permeability of the blood-brain barrier to gp120, the viral coat of HIV-1, exist. The in itial concentration of gp 120 in 10 brain regions correlated with vascular content in young and old mice. Susceptibility to wheatgerm agglutinin (WGA) -induced uptake of gp120, which relates to endothelial cell internalization , varied regionally, with no induction of uptake into the striatum or hypot halamus but with large increases in the cerebellum, cortex, and midbrain. T ransport across the BBB, as measured by the unidirectional influx rate (Ki) , also varied regionally with the hypothalamus, hippocampus, and pons-medul la showing the highest values for Ki and the striatum the lowest. These reg ional variations in the permeability of the BBB to gp 120 could contribute to the inhomogeneous distribution of HIV-1 within the CNS whereas the failu re to see differences with aging suggests other causes underlie the suscept ibility of the elderly to the CNS manifestations of AIDS.