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Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner

In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination ba...

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Autores principales: Cheng, Yan, Kim, Woong-Ki, Wellman, Laurie L., Sanford, Larry D., Guo, Ming-Lei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538758/
https://www.ncbi.nlm.nih.gov/pubmed/34685469
http://dx.doi.org/10.3390/life11101098
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author Cheng, Yan
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
Guo, Ming-Lei
author_facet Cheng, Yan
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
Guo, Ming-Lei
author_sort Cheng, Yan
collection PubMed
description In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders.
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spelling pubmed-85387582021-10-24 Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner Cheng, Yan Kim, Woong-Ki Wellman, Laurie L. Sanford, Larry D. Guo, Ming-Lei Life (Basel) Article In this study, we investigated autophagy, glial activation status, and corticotropin releasing factor (CRF) signaling in the brains of mice after 5 days of sleep fragmentation (SF). Three different brain regions including the striatum, hippocampus, and frontal cortex were selected for examination based on roles in sleep regulation and sensitivity to sleep disruption. For autophagy, we monitored the levels of various autophagic induction markers including beclin1, LC3II, and p62 as well as the levels of lysosomal associated membrane protein 1 and 2 (LAMP1/2) and the transcription factor EB (TFEB) which are critical for lysosome function and autophagy maturation stage. For the status of microglia and astrocytes, we determined the levels of Iba1 and GFAP in these brain regions. We also measured the levels of CRF and its cognate receptors 1 and 2 (CRFR1/2). Our results showed that 5 days of SF dysregulated autophagy in the striatum and hippocampus but not in the frontal cortex. Additionally, 5 days of SF activated microglia in the striatum but not in the hippocampus or frontal cortex. In the striatum, CRFR2 but not CRFR1 was significantly increased in SF-experienced mice. CRF did not alter its mRNA levels in any of the three brain regions assessed. Our findings revealed that autophagy processes are sensitive to short-term SF in a region-specific manner and suggest that autophagy dysregulation may be a primary initiator for brain changes and functional impairments in the context of sleep disturbances and disorders. MDPI 2021-10-16 /pmc/articles/PMC8538758/ /pubmed/34685469 http://dx.doi.org/10.3390/life11101098 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheng, Yan
Kim, Woong-Ki
Wellman, Laurie L.
Sanford, Larry D.
Guo, Ming-Lei
Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title_full Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title_fullStr Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title_full_unstemmed Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title_short Short-Term Sleep Fragmentation Dysregulates Autophagy in a Brain Region-Specific Manner
title_sort short-term sleep fragmentation dysregulates autophagy in a brain region-specific manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8538758/
https://www.ncbi.nlm.nih.gov/pubmed/34685469
http://dx.doi.org/10.3390/life11101098
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