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. 2023 Oct 10;14:1193053. doi: 10.3389/fimmu.2023.1193053

Figure 3.

Figure 3

Modulation of adult neurogenesis by microglia in depressive. In a healthy central nervous system, microglia produce neurotrophic factors, phagocyte redundant neurons, and connections, remove cell debris, and control stem cell proliferation, in this way regulating synaptogenesis and neuronal pruning. In a pathological state, exogenous and endogenous factors such as infections(LPS), stress, and systemic inflammation/metabolic deregulation can induce microglial activation and impaired neurogenesis. (A) Cytokines such as IL-1β, IL-6, and TNF-α, with negative consequences to the HPA axis. (B) CX3CR1 is involved in interactions between microglia and neurons, which may reduce to pro-inflammation cytokine. (C) Inflammatory microglia(M1) also exhibit upregulated IDO, reducing serotonin availability and possibly contributing to neurogenesis in depression. (D) SCFAs、other bacterial metabolites and components of the immune system can affect microglial maturation, activation and function. (E) A neuroprotective microglial phenotype (classically referred to as “M2-like”) activated the BDNF-TrkB-CREB signaling pathway, enhanced neurogenesis, diminished synapse loss in the hippocampus, and contribute to an overall lower level of neuroinflammation. (F–H) Intracellularly, several pathways become activated including the TLR, JAK, and STAT, which will trigger the activation of the NF-κB, downregulate NLRP3, and consequent induction of first-line cytokine production, such as IL-1β, IL-6, and TNF-α. (I) MicroRNAs have been associated with multiple pathways of depression pathophysiology. LPS lipopolysaccharide, TLR toll-like receptor, JAK Janus kinase, STAT signal transducer and activator of transcription, NF-κB nuclear transcription factor-kappa B, NLRP3 nod-like receptor protein 3, IL-1β interleukin-1β, IL-6 interleukin 6, TNF-α tumor necrosis factor-alpha, HPA hypothalamic-pituitary-adrenal, IDO indoleamine 2,3-dioxygenase, CX3CR1 C-X3-C motif chemokine receptor 1, BDNF- TrkB-CREB brain derived neurotrophic factor- tyrosine kinase receptor B- cyclic adenosine monophosphate response element binding protein, SCFAs short chain fatty acids.