Huitron-Resendiz Salvador, Marcondes Maria Cecilia G, Flynn Claudia T, Lanigan Caroline M S, Fox Howard S
Department of Molecular and Integrative Neuroscience, SP30-2030, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15138-43. doi: 10.1073/pnas.0707171104. Epub 2007 Sep 10.
In monkeys infected with simian immunodeficiency virus (SIV), changes in body temperature and locomotor activity occur after the acute retroviral syndrome stage of the disease. However, alterations to the circadian rhythm of these factors in SIV-infected monkeys have not been reported. To determine whether the circadian rhythm of body temperature and locomotor activity are disrupted during SIV infection, we analyzed the temperature and activity patterns of SIV-infected monkeys through different stages of the disease, progressing to SIV encephalitis by using the cosinor model for circadian oscillation. We found that SIV infection resulted in significant impairments of the amplitude and mean of the circadian rhythm of body temperature and activity and in the acrophase of the circadian rhythm for temperature. These alterations were not related to changes observed in the acute febrile response induced after viral inoculation. In animals killed once marked circadian anomalies were evident, microglia infiltration and macrophage accumulation in the hypothalamus were observed. Together, these results clearly demonstrate that SIV infection compromises aspects of circadian regulation in monkeys, with important implications for physiological functions, including cognition, in HIV-infected individuals.
在感染猴免疫缺陷病毒(SIV)的猴子中,体温和运动活动的变化发生在疾病的急性逆转录病毒综合征阶段之后。然而,尚未有关于SIV感染猴子中这些因素昼夜节律变化的报道。为了确定SIV感染期间体温和运动活动的昼夜节律是否受到干扰,我们通过疾病的不同阶段分析了SIV感染猴子的温度和活动模式,并利用余弦分析模型分析昼夜节律,直至进展为SIV脑炎阶段。我们发现,SIV感染导致体温和活动的昼夜节律的振幅、平均值以及体温昼夜节律的峰值相位出现显著受损。这些改变与病毒接种后诱导的急性发热反应中观察到的变化无关。在出现明显昼夜节律异常后处死的动物中,观察到下丘脑有小胶质细胞浸润和巨噬细胞积聚。总之,这些结果清楚地表明,SIV感染损害了猴子昼夜节律调节的多个方面,这对包括认知在内的生理功能在HIV感染个体中具有重要意义。