Department of Neurology, The University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Neurovirol. 2009 Sep;15(5-6):380-9. doi: 10.3109/13550280903350200.
The human immunodeficiency virus type 1 (HIV-1) transgenic (Tg) rat model incorporates a noninfectious viral genome that is under similar regulatory control mechanisms in vivo as those that exist with natural infection in humans. Vitamin A (VA) deficiency in humans has been associated with progressive systemic HIV disease and with impaired cognition in rodent models. The effects on of VA deficiency on the development of behavioral abnormalities with HIV infection have not been previously described. In these studies, wild-type (Wt) and Tg rats maintained on either a normal (VA+) or a VA-deficient (VA-) diet were examined for activity in an open field (horizontal activity, total distance, vertical activity, and rearing) and on rotarod testing. On both open field and rotarod testing, the Tg rats performed worse than the Wt rats, with the most severe deficits noted in the TgVA- animals. Analysis of the specific effects of the presence of the HIV transgene and the diet on the performance on the open field tests showed a dominant effect from the transgene on all of the tests, with an effect from the diet on only the number of rearings. On rotarod testing, effects form both the diet and the transgene were observed at lower speeds, at the highest speeds, and on the accelerating rotarod. These studies therefore demonstrate that behavioral and motor abnormalities can be detected in this model and are likely due to similar mechanisms by which humans infected with HIV might develop cognitive-motor impairment in association with VA deficiency.
人类免疫缺陷病毒 1 型(HIV-1)转基因(Tg)大鼠模型包含一个非传染性病毒基因组,其在体内的调控机制与人类自然感染时的调控机制相似。人类维生素 A(VA)缺乏与进行性全身性 HIV 疾病和啮齿动物模型中的认知障碍有关。VA 缺乏对 HIV 感染发展为行为异常的影响以前尚未描述过。在这些研究中,用正常(VA+)或 VA 缺乏(VA-)饮食饲养的野生型(Wt)和 Tg 大鼠被检查在开放场(水平活动、总距离、垂直活动和竖起)和旋转棒测试中的活动。在开放场和旋转棒测试中,Tg 大鼠的表现均不如 Wt 大鼠,在 TgVA-动物中观察到最严重的缺陷。对存在 HIV 转基因和饮食对开放场测试表现的具体影响的分析表明,转基因对所有测试均具有显性影响,而饮食仅对竖起的次数有影响。在旋转棒测试中,观察到饮食和转基因的影响在较低速度、最高速度和加速旋转棒上。因此,这些研究表明,该模型中可以检测到行为和运动异常,这可能是由于人类感染 HIV 后可能由于 VA 缺乏而发展出认知运动障碍的类似机制所致。