An emerging role for microglia in stress-effects on memory

Stressful experiences evoke, among others, a rapid increase of 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 towards a proinflammatory 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 impairment in memory and memory synapses caused by (prolonged) stress, implicating this cell type as a potential target in stress-related memory impairments.