Abstract
Microglial cells have emerged as crucial players in synaptic plasticity during development and adulthood, and also in neurodegenerative and neuroinflammatory conditions. Here we found that decreased levels of Sirtuin 2 (Sirt2) deacetylase in microglia affects hippocampal synaptic plasticity under inflammatory conditions. The results show that long-term potentiation (LTP) magnitude recorded from hippocampal slices of wild type mice does not differ between those exposed to lipopolysaccharide (LPS), a pro-inflammatory stimulus, or BSA. However, LTP recorded from hippocampal slices of microglial-specific Sirt2 deficient (Sirt2–) mice was significantly impaired by LPS. Importantly, LTP values were restored by memantine, an antagonist of N-methyl-D-aspartate (NMDA) receptors. These results indicate that microglial Sirt2 prevents NMDA-mediated excitotoxicity in hippocampal slices in response to an inflammatory signal such as LPS. Overall, our data suggest a key-protective role for microglial Sirt2 in mnesic deficits associated with neuroinflammation.
Highlights
Neuroinflammation generally refers to the noxious effects caused by immunological activation of microglia and astrocytes in various diseases of the central nervous system (CNS) and in aging (Streit et al, 2004).Microglia are primary innate immune cells, the resident macrophages of the CNS that constantly survey the microenvironment
Upon LPS inflammatory stimulus, Sirtuin 2 (Sirt2)-deficiency in microglia leads to an long-term potentiation (LTP) impairment in hippocampal slices, which can be reversed by prior exposition of hippocampal slices to memantine, an antagonist of NMDA receptor
Our results suggest that microglial Sirt2 prevents NMDA-mediated excitotoxicity in hippocampal slices stimulated with LPS, revealing a key-protective role for microglial Sirt2 in mnesic deficits associated with neuroinflammation
Summary
Microglia are primary innate immune cells, the resident macrophages of the CNS that constantly survey the microenvironment. They are known to play an important role in regulating brain development and in synaptic plasticity, controlling synapse formation, function and elimination during development and adulthood (Lenz and Nelson, 2018; Lee and Chung, 2019). LTP is considered an electro-physiological model for the basic mechanisms involved in learning and memory formation (Bliss and Collingridge, 1993; Martin and Shapiro, 2000) known to be impaired in models of neurodegenerative diseases characterized by mnesic deficits (Martin and Shapiro, 2000; Lynch, 2004)
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