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

Gourmelon, P.; Briet, Dominique; Clarençon, Didier; Court, Langley; Tsiang, H

doi:10.1016/0006-8993(91)90184-w

Cited by 54 publications

(27 citation statements)

References 30 publications

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“…Without the integrity of the processes, neuronal transmission cannot be accomplished. Thus, our results may form the basis for the neuronal dysfunction found in RV-infected individuals (6,7,24). It is not known why only the pathogenic RV, but not the attenuated RV, induced degeneration of neuronal processes.…”

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confidence: 57%

“…Studies of neuronal dysfunction have revealed electroencephalographic abnormalities, including the disappearance of rapid eye movement sleep and the development of pseudoperiodic facial myoclonus (6). Brain electrical activity terminated about 30 min before cardiac arrest, indicating that cerebral death in experimental rabies occurs prior to failure of vegetative functions (6,7).…”

mentioning

confidence: 99%

“…Brain electrical activity terminated about 30 min before cardiac arrest, indicating that cerebral death in experimental rabies occurs prior to failure of vegetative functions (6,7). RV infection of neurons also induces dysfunction of ion channels, for example, reduction in sodium channels and inward rectifier potassium channels (10,11), which could prevent infected neurons from firing action potentials and generating synaptic potentials, resulting in functional impairment.…”

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confidence: 99%

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Degeneration of Neuronal Processes after Infection with Pathogenic, but Not Attenuated, Rabies Viruses

Li¹,

Sarmento²,

2005

J Virol

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The structural alterations of neuronal processes in mice were investigated after the mice were infected with rabies virus (RV). Silver staining of infected brain sections showed severe destruction and disorganization of neuronal processes in mice infected with pathogenic RV but not with attenuated RV. However, neuronal bodies showed very little pathological changes. Electron microscopy revealed the disappearance of intracellular organelles, as well as the disappearance of synaptic structures and vesicles. Infection of primary neurons with pathogenic, but not attenuated, RV resulted in the destruction of neuronal processes and disappearance of microtubule-associated protein 2 and neurofilament immunoreactivity, which suggests that pathogenic RV causes degeneration of neuronal processes possibly by interrupting cytoskeletal integrity.Despite extensive investigation, the mechanism by which rabies virus (RV) infection causes neurological disease and death is still not completely understood (3). RV enters the peripheral nervous system at the bite site by binding to one or more specific neural receptors (14,22,25) with or without local replication (19,21). Once inside neurons, RV is spread by retrograde transport to the spinal cord and then to the brain (4, 12). Clinical signs include severe agitation, depression, hydrophobia, and paralysis followed by impaired consciousness and coma (9). Patients eventually die of circulatory insufficiency, cardiac arrest, and respiratory failure (9, 23). Despite the dramatic and severe clinical course, postmortem examination of rabies patients reveals only a few pathological lesions, such as cerebral edema (18). Inflammatory reactions and other histological lesions are mild with relatively little neuronal loss (15, 18). These observations led to the hypothesis that fatal rabies may result from neuronal dysfunction rather than neuronal damage (24).Studies of neuronal dysfunction have revealed electroencephalographic abnormalities, including the disappearance of rapid eye movement sleep and the development of pseudoperiodic facial myoclonus (6). Brain electrical activity terminated about 30 min before cardiac arrest, indicating that cerebral death in experimental rabies occurs prior to failure of vegetative functions (6, 7). RV infection of neurons also induces dysfunction of ion channels, for example, reduction in sodium channels and inward rectifier potassium channels (10, 11), which could prevent infected neurons from firing action potentials and generating synaptic potentials, resulting in functional impairment. Decreased binding of serotonin (particularly the subtype 5-HT 1D ) to its receptors has also been reported (2). Recent studies of the release of norepinephrine, dopamine, and serotonin in the hippocampi of rats infected with RV indicated that at the terminal stage of the disease, neurons are no longer capable of releasing neurotransmitters at the synaptic junctions (5). Hence, there is evidence of impaired release of neurotransmitters and binding of neurotransmitters to th...

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confidence: 57%

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Degeneration of Neuronal Processes after Infection with Pathogenic, but Not Attenuated, Rabies Viruses

Li¹,

Sarmento²,

2005

J Virol

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“…Changes in sleep have also been determined for prionrelated diseases and for protozoan parasites, but most studies to date have used virus and bacteria as the infectious agent. CNS viral diseases, such as rabies (Gourmelon et al, 1991) or viral encephalitis in rodents after vesicular stomatitis virus infection (Machida et al, 2014), are associated with altered sleep. In these CNS infections, it is difficult to know whether altered sleep is due to direct actions on regulatory mechanisms, or whether it results from virus-induced brain lesions.…”

Section: Animal Modelsmentioning

confidence: 99%

Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity

Irwin

Opp

2016

Neuropsychopharmacol

384

268

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Sleep disturbances including insomnia independently contribute to risk of inflammatory disorders and major depressive disorder. This review and overview provides an integrated understanding of the reciprocal relationships between sleep and the innate immune system and considers the role of sleep in the nocturnal regulation of the inflammatory biology dynamics; the impact of insomnia complaints, extremes of sleep duration, and experimental sleep deprivation on genomic, cellular, and systemic markers of inflammation; and the influence of sleep complaints and insomnia on inflammaging and molecular processes of cellular aging. Clinical implications of this research include discussion of the contribution of sleep disturbance to depression and especially inflammation-related depressive symptoms. Reciprocal action of inflammatory mediators on the homeostatic regulation of sleep continuity and sleep macrostructure, and the potential of interventions that target insomnia to reverse inflammation, are also reviewed. Together, interactions between sleep and inflammatory biology mechanisms underscore the implications of sleep disturbance for inflammatory disease risk, and provide a map to guide the development of treatments that modulate inflammation, improve sleep, and promote sleep health.

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“…However, mechanisms of neuronal dysfunction in rabies virus infection are still not understood. Studies have investigated ion channel dysfunction (12), abnormalities in neurotransmitters (2,3,5), and electroencephalographic changes (9,10) in rabies virus infection, but no consistent abnormality has been identified. Both nitric oxide neurotoxicity and excitotoxicity have been evaluated with experimental animal models of rabies, but no important role has yet been established for these mechanisms (13,27).…”

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confidence: 99%

Structural Abnormalities in Neurons Are Sufficient To Explain the Clinical Disease and Fatal Outcome of Experimental Rabies in Yellow Fluorescent Protein-Expressing Transgenic Mice

Scott

Rossiter

Andrew

et al. 2008

J Virol

101

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Under natural conditions and in some experimental models, rabies virus infection of the central nervous system causes relatively mild histopathological changes, without prominent evidence of neuronal death despite its lethality. In this study, the effects of rabies virus infection on the structure of neurons were investigated with experimentally infected transgenic mice expressing yellow fluorescent protein (YFP) in neuronal subpopulations. Six-week-old mice were inoculated in the hind-limb footpad with the CVS strain of fixed virus or were mock infected with vehicle (phosphate-buffered saline). Brain regions were subsequently examined by light, epifluorescent, and electron microscopy. In moribund CVS-infected mice, histopathological changes were minimal in paraffin-embedded tissue sections, although mild inflammatory changes were present. Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling and caspase-3 immunostaining showed only a few apoptotic cells in the cerebral cortex and hippocampus. Silver staining demonstrated the preservation of cytoskeletal integrity in the cerebral cortex. However, fluorescence microscopy revealed marked beading and fragmentation of the dendrites and axons of layer V pyramidal neurons in the cerebral cortex, cerebellar mossy fibers, and axons in brainstem tracts. At an earlier time point, when mice displayed hind-limb paralysis, beading was observed in a few axons in the cerebellar commissure. Toluidine blue-stained resinembedded sections from moribund YFP-expressing animals revealed vacuoles within the perikarya and proximal dendrites of pyramidal neurons in the cerebral cortex and hippocampus. These vacuoles corresponded with swollen mitochondria under electron microscopy. Vacuolation was also observed ultrastructurally in axons and in presynaptic nerve endings. We conclude that the observed structural changes are sufficient to explain the severe clinical disease with a fatal outcome in this experimental model of rabies.Rabies is an acute viral infection of the central nervous system for which there is no effective antiviral therapy in humans (14). Despite its lethality, only relatively mild histopathological lesions are typically found under natural conditions, leading to the concept that neuronal dysfunction, rather than structural neuronal injury or cell death, is responsible for the clinical features and fatal outcome (8, 13). However, mechanisms of neuronal dysfunction in rabies virus infection are still not understood. Studies have investigated ion channel dysfunction (12), abnormalities in neurotransmitters (2, 3, 5), and electroencephalographic changes (9, 10) in rabies virus infection, but no consistent abnormality has been identified. Both nitric oxide neurotoxicity and excitotoxicity have been evaluated with experimental animal models of rabies, but no important role has yet been established for these mechanisms (13,27). Li and colleagues (19) have suggested that the degeneration of neuronal processes and disruption of synaptic structures may for...

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

Cited by 54 publications

References 30 publications

Degeneration of Neuronal Processes after Infection with Pathogenic, but Not Attenuated, Rabies Viruses

Degeneration of Neuronal Processes after Infection with Pathogenic, but Not Attenuated, Rabies Viruses

Sleep Health: Reciprocal Regulation of Sleep and Innate Immunity

Structural Abnormalities in Neurons Are Sufficient To Explain the Clinical Disease and Fatal Outcome of Experimental Rabies in Yellow Fluorescent Protein-Expressing Transgenic Mice

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