Switching of the Microglial Activation Phenotype Is a Possible Treatment for Depression Disorder

Abstract

Major depressive disorder (MDD) is a common emotional cognitive disorder that seriously affects people’s physical and mental health and their quality of life. Due to its clinical and etiological heterogeneity, the molecular mechanisms underpinning MDD are complex and they are not fully understood. In addition, the effects of traditional drug therapy are not ideal. However, postmortem and animal studies have shown that overactivated microglia can inhibit neurogenesis in the hippocampus and induce depressive-like behaviors. Nonetheless, the molecular mechanisms by which microglia regulate nerve regeneration and determine depressive-like behaviors remain unclear. As the immune cells of the central nervous system (CNS), microglia could influence neurogenesis through the M1 and M2 subtypes, and these may promote depressive-like behaviors. Microglia may be divided into four main states or phenotypes. Under stress, microglial cells are induced into the M1 type, releasing inflammatory factors and causing neuroinflammatory responses. After the inflammation fades away, microglia shift into the alternative activated M2 phenotypes that play a role in neuroprotection. These activated M2 subtypes consist of M2a, M2b and M2c and their functions are different in the CNS. In this article, we mainly introduce the relationship between microglia and MDD. Importantly, this article elucidates a plausible mechanism by which microglia regulate inflammation and neurogenesis in ameliorating MDD. This could provide a reliable basis for the treatment of MDD in the future.

Effect of Toll‐like receptor 4 on depressive‐like behaviors induced by chronic social defeat stress

“…In the present study, we found that CSDS resulted in depressivelike behaviors including increased immobility duration in FST, decreased social interaction ratio in SIT, and decreased time spent in the light area in LDT, accompanied by increased TLR4 protein level in hippocampus. Hippocampus is considered to be one of the most (Kubera, Obuchowicz, Goehler, Brzeszcz, & Maes, 2011;Tang et al, 2016;Zhang, Zhang, & You, 2018;Zhao et al, 2019). In this study, by using the antidepressant fluoxetine, TLR4 inhibitor, and TLR4 knockout Con, control; KO, knockout; SD, stress; TNF-α, tumor necrosis factor-α; TLR4, Toll-like receptor 4; WT, wild-type mice, our results suggest that hippocampal TLR4 is involved in behavioral despair induced by CSDS.…”

“…Hippocampus is considered to be one of the most important areas involved in stress and depression. For example, neuroinflammation, apoptosis, reduced neurogenesis, and dysfunction of microglia in hippocampus are associated with depression (Kubera, Obuchowicz, Goehler, Brzeszcz, & Maes, ; Tang et al, ; Zhang, Zhang, & You, ; Zhao et al, ). In this study, by using the antidepressant fluoxetine, TLR4 inhibitor, and TLR4 knockout mice, our results suggest that hippocampal TLR4 is involved in behavioral despair induced by CSDS.…”

“…Recently, studies indicate that after exposure to stress, microglial cells were induced into the M1 phenotype, which was associated with upregulating pro‐inflammatory cytokines and the onset of psychiatric disorders (Zhang et al, ). TLR4 deficiency could induce microglial polarization toward the M2 phenotype and downregulating pro‐inflammatory cytokines, which may contribute to the prevention of psychiatric disorders (Yao et al, ; Zhang et al, ; Zhao et al, ).…”

The antidepressant effects of asperosaponin VI are mediated by the suppression of microglial activation and reduction of TLR4/NF-ĸB induced IDO expression

“…This result supports our previous hypothesis that the antidepressant effect of ASA Ⅵ is potentially mediated by inhibiting LPS-induced activation of microglia and neuroinflammation. Microglia activation plays an important role in the development of depression (Zhang et al 2018). Neuroinflammatory injury is considered to be one of the main reasons that microglia cells aggravate the pathological process of depression (Zhang et al 2018).…”

Mitochondria could be a potential key mediator linking the intestinal microbiota to depression

“…[19][20][21] Mitochondria have been considered to play key roles in these changes in depression. [19][20][21] Mitochondria have been considered to play key roles in these changes in depression.…”