Prospéro-García O, Herold N, Phillips T R, Elder J H, Bloom F E, Henriksen S J
Department of Neuropharmacology, Scripps Research Institute, La Jolla, CA 92037.
Proc Natl Acad Sci U S A. 1994 Dec 20;91(26):12947-51. doi: 10.1073/pnas.91.26.12947.
Human immunodeficiency virus (HIV)-related sleep disturbances have been reported early in AIDS. Likewise, the feline immunodeficiency virus (FIV), a natural lentivirus pathogen of cats, produces a similar immunodeficiency syndrome with neurological sequelae. To identify the neurophysiological substrate of FIV infection in brain, pathogen-free cats were infected with the Maryland strain of FIV. Eight weeks after inoculation, all FIV-infected cats seroconverted and virus was detected in the cerebrospinal fluid and in the mononuclear cells of peripheral blood. Ten to 12 months after the FIV inoculation, inoculated and control cats were surgically implanted with electrodes to record the sleep/wake cycle. These sleep recordings were obtained under conditions controlling for environmental variables and instrumental adaptation. FIV-infected cats spent 50% more time awake than the sham-inoculated controls and exhibited many more sleep/waking stage shifts--i.e., 40% more than controls. In addition, FIV-infected cats showed approximately 30% of rapid eye movement (REM) sleep reduction compared to controls. The latency to sleep and REM sleep onset was also significantly delayed in FIV-infected cats. In addition, a remarkable increase in cortically recorded spindle activity (8-13 Hz) was observed during slow-wave sleep in some infected subjects, similar to changes described in HIV-infected humans. Moreover, infected cats exhibited no overt signs of systemic morbidity, such as hyperpyrexia or body weight loss. These results indicate that FIV-infected cats exhibit sleep abnormalities similar to the sleep disturbances previously described in AIDS patients and further support the feline preparation as a valuable animal model of HIV infection of the central nervous system.
在艾滋病早期就已报道过与人类免疫缺陷病毒（HIV）相关的睡眠障碍。同样，猫免疫缺陷病毒（FIV）作为猫的一种天然慢病毒病原体，会引发一种伴有神经后遗症的类似免疫缺陷综合征。为了确定脑部FIV感染的神经生理基础，将无病原体的猫感染了马里兰株FIV。接种八周后，所有感染FIV的猫都发生了血清转化，并且在脑脊液和外周血单核细胞中检测到了病毒。在接种FIV后的10至12个月，给接种组和对照组的猫进行手术植入电极，以记录睡眠/觉醒周期。这些睡眠记录是在控制环境变量和仪器适应性的条件下获得的。感染FIV的猫比假接种对照组的猫清醒时间多50%，并且睡眠/觉醒阶段转换更多——即比对照组多40%。此外，与对照组相比，感染FIV的猫的快速眼动（REM）睡眠减少了约30%。感染FIV的猫入睡潜伏期和REM睡眠起始潜伏期也显著延迟。此外，在一些受感染的实验对象的慢波睡眠期间，观察到皮层记录的纺锤波活动（8 - 13赫兹）显著增加，这与HIV感染人类中描述的变化相似。而且接种组的猫没有出现全身性发病的明显迹象，如高热或体重减轻。这些结果表明，感染FIV的猫表现出与先前在艾滋病患者中描述的睡眠障碍相似的睡眠异常，并进一步支持将猫作为HIV感染中枢神经系统的有价值动物模型。
