Regional disease in AMPA receptor density in mice infected with the LP-BM5 murine leukemia virus

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Abstract
THE status of α-amino-3-hydroxy-5-methly-4-isoxizole (AMPA) receptors in several brain regions was investigated in a murine model of retrovirus-associated cognitive impairment, the LP-BM5 infected mouse. The Bmax of [3H]AMPA receptors in the cortex, striatum, hippocampus and cerebellum declined by 29–50% as early as 8 weeks post-inoculation. Immunohistochemistry revealed foci of decreased glutamate receptor (GluR)-2/3 protein expression by Purkinje neurons distributed throughout the cerebellum. Immunoblots indicated that cerebellar expression of only GluR-3 protein was reduced. This global decrease in AMPA receptors may constitute a compensatory response to elevated excitotoxin (glutamate) concentrations 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 associated with infection by retroviruses such as HIV-1.