Frontiers in Neuroscience (Jun 2020)

Microglial Sirtuin 2 Shapes Long-Term Potentiation in Hippocampal Slices

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

DOI
https://doi.org/10.3389/fnins.2020.00614
Journal volume & issue
Vol. 14

Abstract

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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.

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