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

Yan Cheng; Woong-Ki Kim; Laurie L Wellman; Larry D Sanford; Ming-Lei Guo

doi:10.3390/life11101098

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

Life (Basel). 2021 Oct 16;11(10):1098. doi: 10.3390/life11101098.

Authors

Yan Cheng^{1

2

3}, Woong-Ki Kim^{1

4}, Laurie L Wellman^{1

2}, Larry D Sanford^{1

2}, Ming-Lei Guo^{1

3}

Affiliations

¹ Center for Integrative Neuroscience and Inflammatory Diseases, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
² Sleep Research Laboratory, Department of Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
³ Drug Addiction Laboratory, Department Pathology and Anatomy, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
⁴ Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, Norfolk, VA 23507, USA.

Abstract

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.

Keywords: autophagy; corticotropin releasing factor; microglia; neuroinflammation; sleep fragmentation.