Roscoe Robert F, Mactutus Charles F, Booze Rosemarie M
Laboratory of Behavioral Neuroscience, Department of Psychology, University of South Carolina, 29208, Columbia, SC, USA.
J Neuroimmune Pharmacol. 2014 Dec;9(5):642-53. doi: 10.1007/s11481-014-9555-z. Epub 2014 Jul 19.
HIV-1 associated neurocognitive deficits are increasing in prevalence, although the neuronal basis for these deficits is unclear. HIV-1 Tg rats constitutively express 7 of 9 HIV-associated proteins, and may be useful for studying the neuropathological substrates of HIV-1 associated neurocognitive disorders (HAND). In this study, adult female HIV-1 Tg rats and F344 control rats had similar growth rates, estrous cyclicity and startle reflex inhibition to a visual prepulse stimulus. Medium spiny neurons (MSNs) in the nucleus accumbens (NAcc) were ballistically-labeled utilizing the indocarbocyanine dye DiI. The branching complexity of MSNs in the NAcc was significantly decreased in HIV-1 Tg rats, relative to controls; moreover, the shorter length and decreased volume of dendritic spines, but unchanged head diameter, in HIV-1 Tg rats suggested a reduction of longer spines and an increase in shorter, less projected spines, indicating a population shift to a more immature spine phenotype. Collectively, these results from HIV-1 Tg female rats indicated significant synaptodendritic alterations of MSNs in the NAcc occur as a consequence of chronic, low-level, exposure to HIV-1 associated proteins.
尽管HIV-1相关神经认知缺陷的神经元基础尚不清楚,但其患病率正在上升。HIV-1转基因大鼠组成性表达9种HIV相关蛋白中的7种,可能有助于研究HIV-1相关神经认知障碍(HAND)的神经病理学底物。在本研究中,成年雌性HIV-1转基因大鼠和F344对照大鼠在生长速率、发情周期以及对视觉预脉冲刺激的惊吓反射抑制方面相似。利用吲哚花青绿染料DiI对伏隔核(NAcc)中的中等棘状神经元(MSN)进行了弹道标记。相对于对照组,HIV-1转基因大鼠NAcc中MSN的分支复杂性显著降低;此外,HIV-1转基因大鼠中树突棘长度较短、体积减小,但头部直径不变,这表明较长的棘减少,较短、突出较少的棘增加,表明群体向更不成熟的棘表型转变。总体而言,这些来自HIV-1转基因雌性大鼠的结果表明,由于长期低水平暴露于HIV-1相关蛋白,NAcc中的MSN发生了显著的突触树突改变。