CD200 in dentate gyrus improves depressive-like behaviors of mice through enhancing hippocampal neurogenesis via alleviation of microglia hyperactivation

Abstract

Background Neuroinflammation and microglia play critical roles in the development of depression. Cluster of differentiation 200 (CD200) is an anti-inflammatory glycoprotein that is mainly expressed in neurons, and its receptor CD200R1 is primarily in microglia. Although the CD200–CD200R1 pathway is necessary for microglial activation, its role in the pathophysiology of depression remains unknown. Methods The chronic social defeat stress (CSDS) with behavioral tests were performed to investigate the effect of CD200 on the depressive-like behaviors. Viral vectors were used to overexpress or knockdown of CD200. The levels of CD200 and inflammatory cytokines were tested with molecular biological techniques. The status of microglia, the expression of BDNF and neurogenesis were detected with immunofluorescence imaging. Results We found that the expression of CD200 was decreased in the dentate gyrus (DG) region of mice experienced CSDS. Overexpression of CD200 alleviated the depressive-like behaviors of stressed mice and inhibition of CD200 facilitated the susceptibility to stress. When CD200R1 receptors on microglia were knocked down, CD200 was unable to exert its role in alleviating depressive-like behavior. Microglia in the DG brain region were morphologically activated after exposure to CSDS. In contrast, exogenous administration of CD200 inhibited microglia hyperactivation, alleviated neuroinflammatory response in hippocampus, and increased the expression of BDNF, which in turn ameliorated adult hippocampal neurogenesis impairment in the DG induced by CSDS. Conclusions Taken together, these results suggest that CD200-mediated alleviation of microglia hyperactivation contributes to the antidepressant effect of neurogenesis in dentate gyrus in mice.

Wenyang-Tianjing-Jieyu Decoction Improves Depression Rats of Kidney Yang Deficiency Pattern by Regulating T Cell Homeostasis and Inflammation Level

“… 30 In addition, the plasticity of neurons in the hippocampus is high, which is closely related to memory, emotion, and learning function. 31 , 32 Studies have shown that stress can affect the activation of microglia in the hippocampus, which in turn increases the expression of TNF-α in the tissue 33 At the same time, hippocampal CD38 is closely related to depression-like behavior in the inflammatory model. 34 In short, the hippocampus is one of the most studied brain regions in animal models of depression, and it is also considered to be the brain region that is most closely related to depression.…”

“…30 In addition, the plasticity of neurons in the hippocampus is high, which is closely related to memory, emotion, and learning function. 31,32 Studies have shown that stress can affect the activation of https://doi.org/10.2147/NDT.S445636…”

Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets

“…Considering that mice deficient in CX3CR1 have impaired neurogenesis and synaptic plasticity, reduced expression of this chemokine could negatively affect neuroplasticity pathways [ 105 ]. Interestingly, the neuronal glycoprotein cluster of differentiation 200 (CD200) acts in a similar way to CX3CL1 by activating the microglial CD200R1 receptor [ 106 , 107 ]. In a chronic stress model induced by social defeat, the induction of depressive-like behaviors was related to microglial activation and a decrease in CD200 in the hippocampal dentate gyrus.…”

“…In a chronic stress model induced by social defeat, the induction of depressive-like behaviors was related to microglial activation and a decrease in CD200 in the hippocampal dentate gyrus. In contrast, exogenous CD200 treatment alleviated the neuroinflammatory response and increased BDNF expression, which in turn improved hippocampal neurogenesis in this model [ 107 ]. These findings suggest that microglial activation is one of the possible mechanisms underlying the impaired neuroplasticity seen in MDD [ 77 ].…”

Adult hippocampal neurogenesis: pharmacological mechanisms of antidepressant active ingredients in traditional Chinese medicine

“…Stress-induced abnormal activation of microglia can impair the physiological process of neurogenesis, thereby leading to depression-like behavior. Reducing excessive neuroinflammation can ameliorate impaired neurogenesis and serve as a treatment for depression ( Amanollahi et al, 2023 ; Chen et al, 2023 ).…”