不同年龄HIV-1转基因大鼠神经病理学特征
Characterization of neuropathology in the HIV-1 transgenic rat at different ages.
作者信息
Reid William C, Ibrahim Wael G, Kim Saejeong J, Denaro Frank, Casas Rafael, Lee Dianne E, Maric Dragan, Hammoud Dima A
机构信息
Center for Infectious Disease Imaging (CIDI), Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
出版信息
J Neuroimmunol. 2016 Mar 15;292:116-25. doi: 10.1016/j.jneuroim.2016.01.022. Epub 2016 Feb 3.
The transgenic HIV-1 rat (Tg) is a commonly used neuroHIV model with documented neurologic/behavioral deficits. Using immunofluorescent staining of the Tg brain, we found astrocytic dysfunction/damage, as well as dopaminergic neuronal loss/dysfunction, both of which worsening significantly in the striatum with age. We saw mild microglial activation in young Tg brains, but this decreased with age. There were no differences in neurogenesis potential suggesting a neurodegenerative rather than a neurodevelopmental process. Gp120 CSF levels exceeded serum gp120 levels in some animals, suggesting local viral protein production in the brain. Further probing of the pathophysiology underlying astrocytic injury in this model is warranted.
转基因HIV-1大鼠(Tg)是一种常用的神经艾滋病模型,有记录显示其存在神经/行为缺陷。通过对Tg大鼠大脑进行免疫荧光染色,我们发现星形胶质细胞功能障碍/损伤以及多巴胺能神经元丢失/功能障碍,二者均会随着年龄增长在纹状体中显著恶化。我们在年轻的Tg大鼠大脑中观察到轻度的小胶质细胞激活,但这种激活会随着年龄增长而减少。神经发生潜能没有差异,提示这是一个神经退行性过程而非神经发育过程。在一些动物中,脑脊液中Gp120水平超过血清Gp120水平,提示大脑中存在局部病毒蛋白产生。有必要进一步探究该模型中星形胶质细胞损伤的病理生理学机制。