Microglial Responses to Stress-Induced Depression: Causes and Consequences

Chronic stress is a major risk factor for various psychiatric diseases, including depression; it triggers various cellular and structural changes, resulting in the alteration of neurocircuitry and subsequent development of depression. Accumulating evidence suggests that microglial cells orchestrate stress-induced depression. Preclinical studies of stress-induced depression revealed microglial inflammatory activation in regions of the brain that regulate mood. Although studies have identified several molecules that trigger inflammatory responses in microglia, the pathways that regulate stress-induced microglial activation remain unclear. Understanding the exact triggers that induce microglial inflammatory activation can help find therapeutic targets in order to treat depression. In the current review, we summarize the recent literature on possible sources of microglial inflammatory activation in animal models of chronic stress-induced depression. In addition, we describe how microglial inflammatory signaling affects neuronal health and causes depressive-like behavior in animal models. Finally, we propose ways to target the microglial inflammatory cascade to treat depressive disorders.

Automated summary

Chronic stress is a significant risk factor for psychiatric diseases, particularly depression, as it causes cellular and structural changes that affect neurocircuitry and contribute to the development of depression. Recent studies have shown that microglial cells play a role in stress-induced depression through inflammatory activation. The exact pathways involved in stress-induced microglial activation are still unclear, but identifying these triggers can aid in the development of targeted therapies for depression.