TMARC Pilot Studies - Completed

Effects of HIV/Tat Protein Expression on Spatial Learning & Memory in Mice (Kesby)

Agency: TMARC
PI: Kesby, James, Ph.D.

Abstract

HIV-induced neuropathology leads to altered brain dopaminergic function and cognitive deficits such as impaired memory retrieval and cognitive flexibility. Adjunct treatment with selegiline, a monoamine oxidase inhibitor that improves dopamine function, has the potential to improve cognitive function in HIV-infected individuals. HIV-induced cognitive deficits may not depend on viral infection itself but rather on neurotoxic viral products such as HIV/TAT. Transgenic mice with doxycycline-induced TAT protein expression in the brain (iTAT) display a spectrum of neuropathology resembling brain abnormalities in HIV-infected humans; deficits in learning, memory, reversal learning and altered dopaminergic transmission. The goal of the proposed project is to take advantage of the iTAT mouse model to discretely assess memory retention/recall and reversal learning deficits in the Barnes maze test without the confounding influence of deficits in task acquisition (Aim 1). Further, we will assess whether selegiline will reverse predicted deficits in memory retention and reversal learning (Aim 1). Considering that memory retention/recall and reversal learning are sensitive to disruption of corticolimbic dopamine function, dopamine levels in the medial prefrontal cortex, hippocampus and caudate putamen will be measured with High Performance Liquid Chromatography (Aim 2). It is predicted TAT-induced deficits in memory retention/recall and reversal learning will correlate with altered DA levels and that selegiline will improve cognition in iTAT mice by improving dopamine function. Understanding specific deficits in memory and reversal learning in iTAT mice in conjunction with neurochemical analysis may help identify targets for development of adjunct therapies for the treatment of cognitive deficits in HIV-infected patients.

Sponsored by NIH/NIDA P50DA026306

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