REGIONAL DISEASE IN AMPA RECEPTOR DENSITY IN MICE INFECTED WITH THE LP-BM5 MURINE LEUKEMIA-VIRUS

THE status of alpha-amino-3-hydroxy-5-methly-4-isoxizole (AMPA) recept ors in several brain regions was investigated in a murine model of ret rovirus-associaed cognitive impairment, the LP-BM5 infected mouse. The B-max of [H-3]AMPA receptors in the cortex, striatum, hippocampus and cerebellum declined by 29-50% as early as 8 weeks post-inoculation. I mmunohistochemistry revealed foci of decreased glutamate (GluR)-2/3 pr otein expression by Purkinje distributed throughout the cerebellum. Im munoblots indicated that cerebellar expression of only GluR-3 protein was reduced. This global decrease in AMPA receptors may constitute a c ompensatory response to elevated excitotoxin (glutamate) concentration s and are concurrent with the development of spatial learning deficits observed in these mice. Thus, the reduction in AMPA receptor density may contribute to the development of the cognitive abnormalities assoc iated with infection by retroviruses such as HIV-1.