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

An emerging role for microglia in stress-effects on memory

Jeniffer Sanguino-Gómez  1 , Jacobus C Buurstede  2 , Oihane Abiega  1 , Carlos P Fitzsimons  1 , Paul J Lucassen  1 , Bart J L Eggen  3 , Sylvie L Lesuis  1   4 , Onno C Meijer  2 , Harm J Krugers  1
Affiliations
Review

An emerging role for microglia in stress-effects on memory

Jeniffer Sanguino-Gómez et al. Eur J Neurosci. 2022 May.

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.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram depicting major afferent and efferent connections of the autonomic nervous and hypothalamic–pituitary–adrenal (HPA) axis. ACTH: adrenocorticotropic hormone, CRH: Corticotropin release hormone, MR: mineralocorticoid receptor, GR: glucocorticoid receptor
FIGURE 2
FIGURE 2
Association between stress, memory and microglia. Stressful situations can alter the microglia, leading to an (1) increase in number and a (2) shift towards a more proinflammatory profile, that is related to disruptions in memory processing. These microglia are (2) not properly communicating with neurons, which underlie memory malfunction/deficits, and could be mediated by (3) synaptic transmission, and (4) metabolic routes with synaptic‐related metabolites
See this image and copyright information in PMC

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