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Microglial Sirtuin 2 Shapes Long-Term Potentiation in Hippocampal Slices

Joana Sa de Almeida1,2,3, Mariana Vargas2,3, João Fonseca-Gomes2,3

  • 1Division of Development and Growth, Department of Woman, Child and Adolescent, University Hospitals of Geneva, Geneva, Switzerland.

Frontiers in Neuroscience
|July 7, 2020
PubMed

Insights

Microglial Sirtuin 2 (Sirt2) protects against inflammation-induced memory loss. Loss of microglial Sirt2 impairs synaptic plasticity, but memantine restores it, suggesting a key role in preventing excitotoxicity.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Microglial cells are vital in synaptic plasticity and neuroinflammation.
  • Sirtuin 2 (Sirt2) deacetylase activity in microglia is implicated in brain function.

Purpose of the Study:

  • To investigate the role of microglial Sirtuin 2 (Sirt2) in hippocampal synaptic plasticity under inflammatory conditions.
  • To determine if Sirt2 deficiency in microglia exacerbates neuroinflammation-induced memory deficits.

Main Methods:

  • Used lipopolysaccharide (LPS) to induce inflammation in wild-type and microglial-specific Sirt2-deficient mice.
  • Measured long-term potentiation (LTP) in hippocampal slices.
  • Administered memantine, an N-methyl-D-aspartate (NMDA) receptor antagonist.

Main Results:

  • LPS did not affect LTP in wild-type mice.
  • LPS significantly impaired LTP in microglial Sirt2-deficient mice.
  • Memantine restored LTP in Sirt2-deficient mice exposed to LPS.

Conclusions:

  • Microglial Sirtuin 2 (Sirt2) prevents NMDA-mediated excitotoxicity in the hippocampus during inflammation.
  • Microglial Sirt2 plays a crucial protective role against memory deficits in neuroinflammation.
Keywords:
long-term potentiationmemantinemicroglianeuroinfalmmationsirtuin 2

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