Conditional Tat protein expression in the GT-tg bigenic mouse brain induces gray matter density reductions

Abstract

Tat (Trans-activator of transcription) is implicated in the neuropathogenesis of HIV-1 infection and known to contribute to neuronal damage and learning and memory impairments. However, direct neuroanatomical demonstration of Tat pathobiology is limited. GT-tg bigenic mice with a doxycycline (Dox)-inducible and brain-selective tat gene were used to test the hypothesis that conditional induction of Tat activity in brain can induce gray matter density abnormalities. Ultra high spatial resolution ex vivo magnetic resonance imaging (MRI) combined with a voxel based morphometry (VBM) analysis revealed gray matter density reductions in the sublenticular extended amygdala, the amygdala, the amygdala-hippocampal area, piriform and peri-/entorhinal cortices, and hypothalamus, in Tat-expressing GT-tg mice compared to Dox-treated C57Bl/6J mice. These neuroanatomical abnormalities are consistent with regions expected to be abnormal based on behavioral deficits exhibited by Tat-expressing mice (Carey et al., 2012). These experiments provide the first neuroimaging evidence that conditional Tat protein expression in the GT-tg bigenic mouse model alters brain structure. The findings warrant future studies to further characterize effects of conditional Tat expression on brain structure. Such studies may improve our understanding of the neurological underpinnings of neuroAIDS and the neurodegeneration associated with HIV-1 infection, potentially leading to new treatments.