Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV.
Imaging dopaminergic dysfunction as a surrogate marker of neuropathology in a small-animal model of HIV.
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DOI：
10.2310/7290.2014.00031
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发表时间：
2014
影响因子：
2.8
通讯作者：
Hammoud DA
中科院分区：
文献类型：
--
作者：
Lee DE;Reid WC;Ibrahim WG;Peterson KL;Lentz MR;Maric D;Choyke PL;Jagoda EM;Hammoud DA
The dopaminergic system is especially vulnerable to the effects of HIV infection rendering dopaminergic deficits early surrogate markers of HIV-associated neuropathology. We quantified dopamine D2/3 receptors in young HIV-1 transgenic (Tg) (n=6) and age-matched control rats (n=7) and adult Tg (n=5) and age-matched control rats (n=5) using [18F]fallypride PET. Regional uptake was quantified as binding potential (BPND) using the two-tissue reference model with cerebellum as reference. Time activity curves were generated for the ventral striatum (VS), dorsal striatum (DS), thalamus (Th), and cerebellum. While BPND values were significantly lower in the VS (p<0.001) and DS (p=0.001) in the adult Tg rats compared to controls rats, they were significantly lower only in the DS (p<0.05) in the young rats. Tg rats had smaller striatal volumes on MRI. We also found lower expression levels of tyrosine hydroxylase on immunohistochemistry in the Tg animals. Our findings suggest that progressive striatal D2/3 receptor deficits occur in Tg rats as they age and can be detected using small animal PET imaging. Effectiveness of various approaches in preventing/halting this dopaminergic loss in the Tg rat can thus be measured preclinically using [18F]fallypride PET as a molecular imaging biomarker of HIV-associated neuropathology.
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