Chronic sleep fragmentation shares similar pathogenesis with neurodegenerative diseases: Endosome‐autophagosome‐lysosome pathway dysfunction and microglia‐mediated neuroinflammation

Autor: Li-Fang Huang, Wei Wang, Sai-Yue Deng, Fengfei Ding, Si-Miao Chen, Li Ba, Min Wang, Min Zhang, Yi Xie
Rok vydání: 2019
Předmět:
0301 basic medicine
Autophagosome
microglia
Hippocampus
Anxiety
Pathogenesis
Mice
Cognition
0302 clinical medicine
Medicine
Pharmacology (medical)
Late endosome
Microglia
Neurodegeneration
Neurodegenerative Diseases
Alzheimer's disease
Psychiatry and Mental health
medicine.anatomical_structure
lysosome
Encephalitis
Original Article
Signal Transduction
autophagy
Endosomes
03 medical and health sciences
Memory
amyloid‐β
Physiology (medical)
Animals
sleep fragmentation
Maze Learning
Neuroinflammation
rab5 GTP-Binding Proteins
Pharmacology
business.industry
Autophagy
Autophagosomes
rab7 GTP-Binding Proteins
Recognition
Psychology
Original Articles
medicine.disease
Mice
Inbred C57BL
030104 developmental biology
rab GTP-Binding Proteins
Chronic Disease
Immunology
Sleep Deprivation
Lysosomes
business
030217 neurology & neurosurgery
Zdroj: CNS Neuroscience & Therapeutics
ISSN: 1755-5949
1755-5930
Popis: Aims Insufficient sleep has been found to result in varying degrees of cognitive impairment and emotional changes. Sleep was reported probably responsible for cleaning metabolic wastes in brain by increasing extracellular bulk flow. Herein, we propose that chronic sleep insufficiency in young adult wild‐type mice is also linked with dysfunction of intracellular protein degradation pathways and microglia‐mediated neuroinflammation, which are potentially important mechanisms in the initiation of neurodegeneration. Methods We applied the chronic sleep fragmentation (CSF) model to induce chronic sleep insufficiency in wild‐type mice. After 2 months of CSF, cognitive function, amyloid‐β accumulation, dysfunction of endosome‐autophagosome‐lysosome pathway, and microglia activation were evaluated. Results Following CSF, impairment of spatial learning and memory, and aggravated anxiety‐like behavior in mice were identified by behavioral experiments. Increased intracellular amyloid‐β accumulation was observed in cortex and hippocampus. Mechanistically, CSF could significantly enhance the expression of Rab5 (early endosome marker), Rab7 (late endosome marker), as well as LC3B (autophagosome marker), and autophagy‐positive regulatory factors in brain detected by immunofluorescent staining and Western blot. In addition, activation of microglia was evident by enhanced CD68, CD16/32, and CD206 levels after CSF treatment. Conclusions Chronic sleep fragmentation could initiate pathogenetic processes similar to the early stage of neurodegeneration, including dysfunction of endosome‐autophagosome‐lysosome pathway and microglia‐mediated neuroinflammation. Our findings further strengthen the link between chronic sleep insufficiency and the initiation of neurodegeneration even if lack of genetic predisposition.
Databáze: OpenAIRE
Externí odkaz: