An emerging role for microglia in stress-effects on memory

Eur J Neurosci. 2022 May;55(9-10):2491-2518. doi: 10.1111/ejn.15188. Epub 2021 May 4.

Abstract

Stressful experiences evoke, among others, a rapid increase in brain (nor)epinephrine (NE) levels and a slower increase in glucocorticoid hormones (GCs) in the brain. Microglia are key regulators of neuronal function and contain receptors for NE and GCs. These brain cells may therefore potentially be involved in modulating stress effects on neuronal function and learning and memory. In this review, we discuss that stress induces (1) an increase in microglial numbers as well as (2) a shift toward a pro-inflammatory profile. These microglia have (3) impaired crosstalk with neurons and (4) disrupted glutamate signaling. Moreover, microglial immune responses after stress (5) alter the kynurenine pathway through metabolites that impair glutamatergic transmission. All these effects could be involved in the impairments in memory and in synaptic plasticity caused by (prolonged) stress, implicating microglia as a potential novel target in stress-related memory impairments.

Keywords: corticosterone; glucocorticoids; learning; norepinephrine; synapses.

Publication types

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

MeSH terms

  • Glucocorticoids / metabolism
  • Humans
  • Memory Disorders / metabolism
  • Microglia* / metabolism
  • Neuronal Plasticity* / physiology
  • Neurons / metabolism

Substances

  • Glucocorticoids