Cognitive and Motor Impairments Associated with SIV Infection in Rhesus Monkeys

Murray, Elisabeth A.; Rausch, Dianne M.; Lendvay, Judit; Sharer, Leroy R.; Eiden, Lee E.

doi:10.1126/science.1546323

Cited by 162 publications

(90 citation statements)

References 17 publications

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“…CNS disease in HIV infection frequently is associated with psychomotor slowing as well as impaired fine and gross motor function (12,13,16). In a study of cognitive and motor impairment in SIV-infected rhesus monkeys, motor skills were the most consistent impairment found (21,39). We also have found that SIV infection can result in transient periods of poor performance over the course of infection as well as sustained abnormalities in the later stages of disease (23).…”

Section: Discussionmentioning

confidence: 93%

“…SIV has been shown to cause an AIDS-like immune deficiency and CNS infection when inoculated into rhesus monkeys (19,20). We and others have demonstrated functional CNS deficiencies in SIV-infected rhesus monkeys, including abnormalities in sensory-evoked potentials, behavioral͞cognitive abnormalities, and motor problems (21)(22)(23). Here we focus on the examination of multiple physiological parameters during the early states of SIV infection of rhesus monkeys.…”

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confidence: 99%

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Early physiological abnormalities after simian immunodeficiency virus infection

Horn

Huitrón‐Reséndiz

Weed

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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Central nervous system (CNS) damage and dysfunction are devastating consequences of HIV infection. Although the CNS is one of the initial targets for HIV infection, little is known about early viral-induced abnormalities that can affect CNS function. Here we report the detection of early physiological abnormalities in simian immunodeficiency virus-infected monkeys. The acute infection caused a disruption of the circadian rhythm manifested by rises in body temperature, observed in all five individuals between 1 and 2 weeks postinoculation (p.i.), accompanied by a reduction in daily motor activity to 50% of control levels. Animals remained hyperthermic at 1 and 2 months p.i. and returned to preinoculation temperatures at 3 months after viral inoculation. Although motor activity recovered to baseline values at 1 month p.i., activity levels then decreased to approximately 50% of preinoculation values over the next 2 months. Analysis of sensory-evoked responses 1 month p.i. revealed distinct infection-induced changes in auditory-evoked potential peak latencies that persisted at 3 months after viral inoculation. These early physiological abnormalities may precede the development of observable cognitive or motor deficiencies and can provide an assay to evaluate agents to prevent or alleviate neuronal dysfunction.

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Section: Discussionmentioning

confidence: 93%

mentioning

confidence: 99%

Early physiological abnormalities after simian immunodeficiency virus infection

Horn

Huitrón‐Reséndiz

Weed

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Disruptions in progressive-ratio performance measured in short probe sessions result from decreases in overall rates of responding and can be interpreted to reflect both motor slowing and a reduction in motivation to work for food. Cognitive and motor impairments have also been reported in monkeys infected with a different strain of SIV (31). A convergence of evidence from electrophysiological and neuropsychological measurements will help to fully characterize the neurological changes associated with SIV infection.…”

Section: Infiltrating T Cellsmentioning

confidence: 99%

Microglia-passaged simian immunodeficiency virus induces neurophysiological abnormalities in monkeys

Prospéro-Garcı́a

Gold

Fox

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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Four rhesus macaques were inoculated intravenously with a cryopreserved stock of microglia obtained from a simian immunodeficiency virus (SIV)-infected rhesus macaque. Before infection, three of the four monkeys were trained and tested daily on a computerized neuropsychological test battery. After SIV infection, behavioral testing continued to monitor deficits associated with disease progression. Five additional age-matched, behaviorally trained monkeys served as controls. Neurophysiological testing for visual and auditory evoked responses was accomplished 37-52 weeks after infection in all monkeys. Subsequently, all four SIVinfected monkeys and one control subject were sacrificed, and samples of brain tissue were taken for pathological analysis. SIV-infected monkeys demonstrated abnormal responses in both auditory and visual evoked responses. In addition, around the time of electrophysiological recording, all three SIV-infected, behaviorally trained monkeys exhibited significant decreases in progressive-ratio performance, ref lecting a reduction in reinforcer efficacy. One subject also demonstrated impairments in shifting of attentional set and motor ability at that time. Neuropathological evaluation revealed that all four SIV-infected monkeys exhibited numerous perivascular and parenchymal infiltrating T cells. These findings document that SIV causes electrophysiological, behavioral, and neuropathological sequelae similar to what has been observed in the human neuroAIDS syndrome. Our observations further validate the simian model for the investigation of the pathogenesis of AIDS dementia and for the investigation of drugs with potential therapeutic benefits.

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“…The cognitive tasks were as follows: (1) delayed matching-to-sample with new stimuli on every trial to test visual recognition memory; (2) delayed matching-to-sample with two repeatedly used stimuli to test recent memory, (3) a visual discrimination learning and retention task to test stimulus-response association, and (4) a spatial scene learning task, which measured long-term memory for spatial locations. The motor task assessed the ability of each monkey to retrieve food from a rotating table (via the turntable speed at which animals successfully retrieved food in 50% of trials) [41].…”

Section: Development Of the Siv Animal Modelmentioning

confidence: 99%

“…The tasks were selected for their breadth in capturing neuropsychological impairments, including those described in HIV-infected humans, and for their ability to target neural substrates well characterized in primate lesioning experiments and implicated in HAD [41,37]. The tasks assessed cognitive and motor function.…”

Section: Development Of the Siv Animal Modelmentioning

confidence: 99%