How Stress Shapes Neuroimmune Function: Implications for the Neurobiology of Psychiatric Disorders

Abstract

Chronic stress causes physiological and hormonal adaptations that lead to neurobiological consequences and behavioral and cognitive impairments. In particular, chronic stress has been shown to drive reduced neurogenesis and altered synaptic plasticity in brain regions that regulate mood and motivation. The neurobiological and behavioral effects of stress resemble the pathophysiology and symptoms observed in psychiatric disorders, suggesting that there are similar underlying mechanisms. Accumulating evidence indicates that neuroimmune systems, particularly microglia, have a critical role in regulating the neurobiology of stress. Preclinical models indicate that chronic stress provokes changes in microglia phenotype and increases inflammatory cytokine signaling, which affects neuronal function and leads to synaptic plasticity deficits and impaired neurogenesis. More recent work has shown that microglia can also phagocytose neuronal elements and contribute to structural remodeling of neurons in response to chronic stress. In this review we highlight work by the Duman research group (as well as others) that has revealed how chronic stress shapes neuroimmune function and, in turn, how inflammatory mediators and microglia contribute to the neurobiological effects of chronic stress. We also provide considerations to engage the therapeutic potential of neuroimmune systems, with the goal of improving treatment for psychiatric disorders.