Sleep alterations in experimental street rabies virus infection occur in the absence of major EEG abnormalities

Abstract

Brain electrical activity and sleep organization were investigated in chronically implanted mice during street rabies virus infection. Continuous EEG recordings showed no gross electrical abnormalities until a few hours before the fatal issue. In contrast, alterations of sleep stages were observed at an early stage during the course of rabies virus infection, at a time when clinical signs were absent. Quantification by spectral analysis showed that the main feature was the early decrease of REM-sleep stages and the increase of the duration of waking stages. Neuromuscular disorders which could occur early were also observed during the disease. Comparison of these data with those obtained from fixed rabies virus infection shows that in the latter the EEG recordings demonstrated early alterations and a progressive deterioration with disappearance of both sleep and waking stages, which were replaced by a pathological sleep stage. In order to evaluate the potential role of the host-specific immune response in promoting brain electrophysiological alterations, EEG recordings and spectral analysis were also performed in cyclophosphamide-treated mice. Street rabies virus-infected and immunosuppressed mice showed identical physiopathological changes as those observed in immunocompetent mice. The implication of these viral-induced electrophysiological alterations in the context of the pathogenic mechanisms of rabies virus is discussed.