Cerebral white matter changes including tissue water diffusion abnormalities
detected with diffusion tensor magnetic resonance imaging (DTI) are commonly found in
humans with Human Immunodeficiency Virus (HIV) infection, as well as in animal models
of the disorder. The severities of some of these abnormalities have been reported to correlate
with measures of disease progression or severity, or with the degree of cognitive dysfunction.
Accordingly, DTI may be a useful translational biomarker. HIV-Tat protein appears to be an
important factor in the viral pathogenesis of HIV-associated neurotoxicity. We previously
reported cerebral gray matter density reductions in the GT-tg bigenic mouse treated with
doxycycline (Dox) to conditionally induce Tat protein expression. Presently, we administered
intraperitoneal (i.p.) Dox (100 mg/kg/day) for 7 days to GT-tg mice to determine whether
induction of conditional Tat expression led to the development of cerebral DTI abnormalities.
Perfused and fixed brains from eight GT-tg mice administered Dox and eight control mice
administered saline i.p. were extracted and underwent DTI scans on a 9.4 Tesla scanner. A whole brain analysis detected
fractional anisotropy (FA) reductions in several areas including insular and endopiriform regions, as well as within the
dorsal striatum. These findings suggest that exposure to Tat protein is sufficient to induce FA abnormalities, and further
support the use of the GT-tg mouse to model some effects of HIV.
Keywords: Diffusion tensor imaging, fractional anisotropy, GT-tg mouse, HIV, Tat.
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