Disrupted sleep without sleep curtailment induces sleepiness and cognitive dysfunction via the tumor necrosis factor-α pathway
| Autor: | Richard C. Li, Vijay Ramesh, Navita Kaushal, Foaz Kayali, Yang Wang, Shelley X. L. Zhang, Deepti Nair, Fahed Hakim, Alba Carreras, David Gozal |
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| Jazyk: | angličtina |
| Předmět: |
Male
medicine.medical_specialty Neurology Immunology Excessive daytime sleepiness Sleep fragmentation lcsh:RC346-429 Mice 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Recurrence Internal medicine Neural Pathways medicine Animals Maze Learning lcsh:Neurology. Diseases of the nervous system 030304 developmental biology Mice Knockout 0303 health sciences Sleep Stages Tumor Necrosis Factor-alpha Research General Neuroscience Sleep apnea Brain medicine.disease Antibodies Neutralizing Sleep in non-human animals Mice Inbred C57BL Obstructive sleep apnea ATP Sleep deprivation Endocrinology Receptors Tumor Necrosis Factor Type I TNF-α Knockout mouse Sleep Deprivation medicine.symptom Arousal Cognition Disorders Psychology 030217 neurology & neurosurgery Signal Transduction Neurocognitive impairments |
| Zdroj: | Journal of Neuroinflammation, Vol 9, Iss 1, p 91 (2012) Journal of Neuroinflammation |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/1742-2094-9-91 |
| Popis: | Background Sleepiness and cognitive dysfunction are recognized as prominent consequences of sleep deprivation. Experimentally induced short-term sleep fragmentation, even in the absence of any reductions in total sleep duration, will lead to the emergence of excessive daytime sleepiness and cognitive impairments in humans. Tumor necrosis factor (TNF)-α has important regulatory effects on sleep, and seems to play a role in the occurrence of excessive daytime sleepiness in children who have disrupted sleep as a result of obstructive sleep apnea, a condition associated with prominent sleep fragmentation. The aim of this study was to examine role of the TNF-α pathway after long-term sleep fragmentation in mice. Methods The effect of chronic sleep fragmentation during the sleep-predominant period on sleep architecture, sleep latency, cognitive function, behavior, and inflammatory markers was assessed in C57BL/6 J and in mice lacking the TNF-α receptor (double knockout mice). In addition, we also assessed the above parameters in C57BL/6 J mice after injection of a TNF-α neutralizing antibody. Results Mice subjected to chronic sleep fragmentation had preserved sleep duration, sleep state distribution, and cumulative delta frequency power, but also exhibited excessive sleepiness, altered cognitive abilities and mood correlates, reduced cyclic AMP response element-binding protein phosphorylation and transcriptional activity, and increased phosphodiesterase-4 expression, in the absence of AMP kinase-α phosphorylation and ATP changes. Selective increases in cortical expression of TNF-α primarily circumscribed to neurons emerged. Consequently, sleepiness and cognitive dysfunction were absent in TNF-α double receptor knockout mice subjected to sleep fragmentation, and similarly, treatment with a TNF-α neutralizing antibody abrogated sleep fragmentation-induced learning deficits and increases in sleep propensity. Conclusions Taken together, our findings show that recurrent arousals during sleep, as happens during sleep apnea, induce excessive sleepiness via activation of inflammatory mechanisms, and more specifically TNF-α-dependent pathways, despite preserved sleep duration. |
| Databáze: | OpenAIRE |
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