Microglial-driven changes in synaptic plasticity: A possible role in major depressive disorder

Psychoneuroendocrinology. 2019 Apr:102:236-247. doi: 10.1016/j.psyneuen.2018.12.233. Epub 2018 Dec 22.

Abstract

Recent data gathered from both in vitro and in vivo models of Major Depressive Disorder (MDD) have indicated that microglia play an active role in modifying some of the most important sources for neuronal plasticity, specifically long-term potentiation (LTP) and long-term depression (LTD). In addition, microglia have been implicated in neuro-immune interaction dysregulations, which are considered a core constituent of MDD pathology. While prior studies have investigated the diverse effects activated microglia can have in the context of depression, including regulation of inflammatory cytokine production and structural changes, recent evidence has revealed a more direct relationship between microglial activation and changes in synaptic function and plasticity, including LTP and LTD. Here we review these findings from animal models, as well as discuss how current preclinical evidence might shed light on novel therapeutic targets for patients with depressive disorder.

Keywords: Depression; LTD; LTP; Microglia; Plasticity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Animals
  • Brain-Derived Neurotrophic Factor / metabolism
  • Chemokine CX3CL1 / metabolism
  • Depressive Disorder, Major / metabolism*
  • Excitatory Postsynaptic Potentials
  • Humans
  • Long-Term Potentiation / physiology
  • Long-Term Synaptic Depression / physiology
  • Microglia / pathology*
  • Neuronal Plasticity / physiology*
  • Reactive Oxygen Species / metabolism
  • Receptors, N-Methyl-D-Aspartate

Substances

  • Brain-Derived Neurotrophic Factor
  • Chemokine CX3CL1
  • Reactive Oxygen Species
  • Receptors, N-Methyl-D-Aspartate
  • BDNF protein, human
  • Adenosine Triphosphatases