Altered brain gene expression and neuron loss in FIV

Ohio State University, Columbus OH

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Abstract

DESCRIPTION (Adapted from the applicant's abstract): Neurological disease is recognized prior to overt acquired immunodeficiency syndrome in HIV infection. The mechanism of early neurologic injury needs study to address basic questions of neuro-AIDS pathogenesis. Whether the neurological deficits seen in AIDS is due to cumulative injury beginning in the asymptomatic phase, or whether separate mechanisms are activated at later infection stages can be determined only when early mechanisms are known. Clinical development of FIV infection closely models HIV disease. The project hypothesis is that persistent alterations in glutamate metabolism in the brain cause progressive neuronal injury during the asymptomatic phase of FIV infection of the cat. Four specific aims will 1) study the kinetics of neuronal loss in asymptomatic phase FIV infection with unbiased methods, 2) use quantitative polymerase chain reaction (PCR) to show brain viral load is constantly low in this phase, 3) analyze RNA and protein expression of astrocytic glutamate transporter GLT-1, and 4) examine a neural culture model for energy deficit.