Microglial Over-Activation by Social Defeat Stress Contributes to Anxiety- and Depressive-Like Behaviors

Abstract

Hyper activation of the neuroimmune system is strongly related to the development of neuropsychiatric disorders. Psychosocial stress has been postulated to play an important role in triggering anxiety and major depression. In preclinical models, there is mounting evidence that social defeat stress activates microglial cells in the central nervous system. This type of stress could be one of the major factors in the development of these psychopathologies. Here, we reviewed the most recent literature on social defeat and the associated immunological reactions. We focused our attention on microglial cells and kept the effect of social defeat over microglia separate from the effect of this stressor on other immune cells and the influence of peripheral immune components in priming central immune reactions. Furthermore, we considered how social defeat stress affects microglial cells and the consequent development of anxiety- and depressive-like states in preclinical studies. We highlighted evidence for the negative impact of the over-activation of the neuroimmune system, especially by the overproduction of pro-inflammatory mediators and cytotoxins. Overproduction of these molecules may cause cellular damage and loss or decreased function of neuronal activity by excessively pruning synaptic connections that ultimately contribute to the development of anxiety- and depressive-like states.

CircDYM ameliorates depressive-like behavior by targeting miR-9 to regulate microglial activation via HSP90 ubiquitination

“…Microglial activation with subsequent inflammatory cytokine release also mediates the effects of stress [29][30][31]; these processes have been implicated as a major trigger of depression in both human and animal models [32][33][34]. At different stages of depression, the functional status of microglia is diverse, and they exert different regulatory effects on neurons in different functional states [30,31,35].…”

P2Y12 deficiency in mouse impairs noradrenergic system in brain, and alters anxiety‐like neurobehavior and memory

“…Recently, there are several studies disclosed its potential on the progression of neurological diseases, such as multiple sclerosis and neuropathic pain, by modulating the function of dendritic cells and microglial cells. Latest reports suggest that microglial cells are actively engaged in the regulation of emotional behavior . Moreover, it has been reported that microglial P2Y 12 is essential for the modulation of synaptic plasticity in mouse visual cortex .…”

“…Latest reports suggest that microglial cells are actively engaged in the regulation of emotional behavior. 9,10 Moreover, it has been reported that microglial P2Y 12 is essential for the modulation of synaptic plasticity in mouse visual cortex. 11 Therefore, it is possible that P2Y 12 may be involved in the regulation of neurobehavior such as emotion and cognition.…”

Genome-wide DNA methylation investigation of stress

“…The HPA axis and the immune system are interconnected and communicate with the central nervous system 282 . Both are implicated in stress-related disorders, as alterations of these systems occur both in peripheral tissues and in the brain with stress exposure [282][283][284][285] . In suicide victims with MDD, an increase in proinflammatory cytokines, hyperactivated microglia, and elevated brain macrophages have been seen [286][287][288] .…”