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Publication Abstract Display
Type: Poster
Title: Independent and combined effects of methamphetamine and HIV gp120 protein on neural microstructure in mice using diffusion tensor imaging.
Authors: McKenna B, Brown GG, Archibald S, Scadeng M, Bussell R, Kesby J, Markou A, Semenova S, the TMARC Group
Date: 10-17-2015
Abstract:Methamphetamine (METH) abuse is common among individuals infected by human immunodeficiency virus (HIV). METH and HIV cause injury to both cortical and subcortical brain regions. However, it is unclear what the independent versus combined effects of HIV and METH are on brain microstructure. The expression of HIV gp120 protein induces neuropathology in mice similar to HIV-induced pathology in humans. Here, we used in vivo diffusion tensor imaging (DTI) to examine 27 gp120-transgenic and 27 non-transgenic mice of which 14 in each group underwent an escalating METH binge or saline control regimen. We examined the independent and combined effects of HIV gp120 protein and METH on microstructural integrity of neural tissue as measured by mean diffusivity. DTI was conducted 3-4 months post-regimen when mice were 9-10 months old. Mean diffusivity maps were calculated and data were aligned to atlas space for analyses. Multiple linear regression with an orthogonal set of contrast codes designed to examine independent and combined effects were used with the following comparisons: 1) control mice vs. the three involved groups; 2) dual gp120/METH vs. gp120 only and METH only mice; and 3) gp120 only vs. METH only mice. A corrected p-value for multiple comparisons of 0.05 was used for all analyses. Compared to the control group, the combined METH, gp120, and dual gp120/METH groups demonstrated increased mean diffusivity within bilateral hippocampi, genu of the corpus callosum, and posterior isocortex. Similar increases in diffusivity were found across groups in hippocampi. Compared to METH only and gp120 only groups, dual gp120/METH mice had increased diffusivity in bilateral midbrain, right hypothalamus, entorhinal cortex, globus pallidus, and caudate. Increased diffusivity was observed in METH only relative to gp120 only within bilateral caudate, right internal capsule, left globus pallidus and hippocampus; whereas increased diffusivity in gp120 only relative to METH only was observed in right midbrain, left thalamus, and genu of the corpus callosum. The results highlight both spatially distinct independent and combined effects of METH and HIV protein gp120 on DTI-measured mean diffusion. METH had a larger impact on the striatum relative to gp120, whereas gp120 had larger relative impact on midbrain and diencephalic nuclei. Combined METH and gp120 led to further increases in mean diffusivity in some, but not all these regions. Hippocampi were affected by both METH and gp120, but not additively. Increased mean diffusion in these regions reflect damage to cell bodies and/or their processes suggesting METH and gp120 may impact the brain through overlapping and distinct mechanisms.

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