Neurological Disorders

A Role for Microglia in Repeated Stress-Induced Functional Changes in the Medial Prefrontal Cortex in Rodents

Abstract

Shiho Kitaoka and Tomoyuki Furuyashiki

In rodents, repeated stress alters the function of the medial prefrontal cortex (mPFC), associated with dendritic atrophy and synaptic loss, leading to emotional and cognitive changes. Roles for monoamines, namely dopamine and noradrenaline, have been implicated in this process. Thus, dopaminergic activity in the mPFC confers stress resilience, and repeated social defeat stress attenuates this dopaminergic activity, leading to social avoidance. In contrast, the activation of adrenergic receptors promotes emotional and cognitive changes induced by repeated stress. Especially, adrenergic signaling in the mPFC during stress exposure is critical for a decline in an mPFC-dependent behavioral performance after repeated stress. Repeated stress activates microglia in multiple brain areas, and recent studies have suggested a link between microglial activation and monoaminergic functions in repeated stress. For example, blockade of β-adrenergic receptors impairs microglial activation by repeated stress. It has also been suggested that stress-activated microglia release prostaglandin (PG) E2 , an inflammation-related molecule that attenuates mPFC dopaminergic activity and causes behavioral depression. Recent studies in non-stressed mice have shown that microglial processes can directly contact with neuronal structures in an activity-dependent manner, leading to structural remodeling of neurons. Since repeated stress activates microglia in multiple brain areas including the mPFC, we hypothesize that microglia may play direct and indirect roles in stress-induced alteration in mPFC functions