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

Jun 4, 2021Behavioural brain research

Long-term sleep loss worsens thinking and brain connection problems in Alzheimer's model mice

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Abstract

Chronic sleep deprivation (SD) for 20 hours daily over 21 days significantly exacerbated cognitive impairments in APP/PS1 transgenic mice.

Chronic SD led to worsened cognitive deficits in APP/PS1 mice, a model for Alzheimer's disease.
The study observed decreased levels of PSD95, a protein associated with synaptic function, following chronic SD.
Increased amyloid-β protein deposition and overactivation of microglia were noted in the hippocampus of APP/PS1 mice after chronic SD.
Hippocampal long-term potentiation (LTP) suppression was aggravated in APP/PS1 mice due to chronic SD.
Chronic SD also impaired cognitive functions and synaptic plasticity in wild type mice through similar mechanisms.

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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.

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

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