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Conditional knockout of AIM2 in microglia ameliorates synaptic plasticity and spatial memory deficits in a mouse model of Alzheimer's disease
- Publication Year :
- 2023
- Publisher :
- Research Square Platform LLC, 2023.
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Abstract
- Alzheimer’s disease (AD) is the most common neurodegenerative disease, and the underlying mechanisms remain unclear. Synaptic dysfunction is a hallmark pathology of AD and is strongly associated with cognitive impairment in AD. Abnormal phagocytosis by microglia is one of the main causes of synapse loss in AD. Existing studies have revealed that inflammasomes contribute to cognitive deficits in AD. Previous studies have shown that the absent in melanoma 2 (AIM2) inflammasome was upregulated in the hippocampus of APP/PS1 mice. In this study, we identified abnormally increased expression of AIM2 in microglia in an Aβ1-42-induced AD mouse model (AD mice). Conditional knockout of microglial AIM2 rescued cognitive impairment and synaptic dysfunction in AD mice. Excessive microglial phagocytosis of synapses was decreased after knockout of microglial AIM2, which was dependent on inhibiting complement activation. These results suggest that microglial AIM2 plays a critical role in regulating synaptic plasticity and memory deficits associated with AD, providing a new direction for developing novel preventative and therapeutic interventions for this disease.
Details
- Database :
- OpenAIRE
- Accession number :
- edsair.doi...........ae9dd7df9422dcd53cb98bd80e74bcbb