AUTHOR=Sa de Almeida Joana , Vargas Mariana , Fonseca-Gomes João , Tanqueiro Sara Ramalho , Belo Rita F. , Miranda-Lourenço Catarina , Sebastião Ana M. , Diógenes Maria José , Pais Teresa F. 

TITLE=Microglial Sirtuin 2 Shapes Long-Term Potentiation in Hippocampal Slices

JOURNAL=Frontiers in Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2020.00614

DOI=10.3389/fnins.2020.00614

ISSN=1662-453X

ABSTRACT=<p>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<sup>–</sup>) 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.</p>