Chronic sleep deprivation exacerbates cognitive and synaptic plasticity impairments in APP/PS1 transgenic mice

• Published in: Behavioural brain research Vol. 412; p. 113400
• Main Authors: Wang, Chun, Gao, Wen-Rui, Yin, Jing, Wang, Zhao-Jun, Qi, Jin-Shun, Cai, Hong-Yan, Wu, Mei-Na
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 27.08.2021
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - physiopathology; Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid-β; Animals; APP/PS1 transgenic mice; Chronic sleep deprivation; Cognition - physiology; Cognition Disorders - etiology; Cognitive behavior; Cognitive Dysfunction - metabolism; Disease Models, Animal; Hippocampus - metabolism; Long-term potentiation; Male; Memory Disorders - pathology; Mice; Mice, Transgenic; Microglia; Neuronal Plasticity - physiology; Plaque, Amyloid - pathology; Presenilin-1 - genetics; Presenilin-1 - metabolism; Sleep - physiology; Sleep Deprivation - physiopathology; Cognitive behavior; Chronic sleep deprivation; APP/PS1 transgenic mice; Amyloid-β; Long-term potentiation; Microglia
• DOI: 10.1016/j.bbr.2021.113400
• ISSN: 0166-4328; 1872-7549

•Chronic sleep deprivation (SD) aggravates the cognitive impairments in APP/PS1 mice.•Chronic SD exacerbates in vivo hippocampal LTP suppression in APP/PS1 mice.•Chronic SD down-regulates the expression level of PSD-95 in the hippocampus of APP/PS1 mice.•Chronic SD increases Aβ deposition and microglia activation in the hippocampus of APP/PS1 mice. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive deficits. Sleep deprivation (SD) could lead to memory deficits, and it was a candidate risk factor for AD. However, the effects of chronic SD on the cognitive functions of AD model mice and its possible mechanism are still unclear. In the present study, 8-month-old male APP/PS1 transgenic mice and wild type (WT) littermates were subjected to chronic SD by using the modified multiple platform method (MMPM), with 20 h of SD each day for 21 days. Then, the effects of chronic SD on cognitive functions in APP/PS1 mice were tested by using behavioral tests, the potential mechanisms were investigated by in vivo electrophysiological recording, western blot and immunochemistry. The results showed that chronic SD obviously aggravated the cognitive impairments, exacerbated in vivo hippocampal long-term potentiation (LTP) suppression, reduced the expression level of PSD95, increased amyloid-β (Aβ) protein deposition and overactivated microglia in the hippocampus of APP/PS1 mice. These results indicate that chronic SD exacerbates the cognitive deficits in APP/PS1 mice by accelerating the development of AD pathologies, reducing the expression of PSD95 and aggravating the LTP suppression in hippocampus. At the same time, chronic SD also impaired cognitive functions and synaptic plasticity in WT mice through down-regulating the level of PSD95 and activating microglia. These findings further clarify the electrophysiological and molecular mechanisms of exacerbated cognitive deficits in AD caused by chronic SD.