Deficiency of Glycosylated α-Dystroglycan in Ventral Hippocampus Bridges the Destabilization of Gamma-Aminobutyric Acid Type A Receptors With the Depressive-like Behaviors of Male Mice

Xie, Wenlong; Zheng, Hongchen; Li, Hou-Hong; Lu, Jia-Jing; Xue, Shi-Ge; Luo, Yi; Ma, Cong; Liu, Jianfeng; Hu, Zhuang-Li; Ni, Lan; You, Jing; Wang, Fang; Chen, Jianguo

doi:10.1016/j.biopsych.2021.10.022

Cited by 14 publications

(15 citation statements)

References 63 publications

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“…Western blotting was performed according to the standard protocol [ 37 ]. Brain tissues were homogenized in RIPA lysis buffer (50 mM Tris–HCl, pH 7.4, 1% NP-40, 0.5% Na-deoxycholate, 0.1% sodium dodecyl sulfate (SDS), 150 mM NaCl, 2 mM EDTA and 50 mM NaF) containing phosphatase inhibitors (Sigma-Aldrich, St. Louis, MO, USA) and protease inhibitors (Roche, Basel, Switzerland).…”

Section: Methodsmentioning

confidence: 99%

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

Chen

Cui

et al. 2023

J Neuroinflammation

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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.

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Section: Methodsmentioning

confidence: 99%

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

Chen

Cui

et al. 2023

J Neuroinflammation

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“…α-DG is required for homeostatic synaptic plasticity by increasing GABAergic currents following prolonged elevation of neuronal activity in hippocampus ( Pribiag et al, 2014 ). Furthermore, chronic stress downregulates α-DG expression in ventral hippocampus ( Xie et al, 2022 ). In-vivo administration of agrin, a dystroglycan ligand, rescues the stress-induced behavioral impairments.…”

Section: Function Of Neurexin Binding Partners At Inhibitory Synapsesmentioning

confidence: 99%

Neurexins and their ligands at inhibitory synapses

Boxer

Aoto

2022

Front. Synaptic Neurosci.

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Since the discovery of neurexins (Nrxns) as essential and evolutionarily conserved synaptic adhesion molecules, focus has largely centered on their functional contributions to glutamatergic synapses. Recently, significant advances to our understanding of neurexin function at GABAergic synapses have revealed that neurexins can play pleiotropic roles in regulating inhibitory synapse maintenance and function in a brain-region and synapse-specific manner. GABAergic neurons are incredibly diverse, exhibiting distinct synaptic properties, sites of innervation, neuromodulation, and plasticity. Different classes of GABAergic neurons often express distinct repertoires of Nrxn isoforms that exhibit differential alternative exon usage. Further, Nrxn ligands can be differentially expressed and can display synapse-specific localization patterns, which may contribute to the formation of a complex trans-synaptic molecular code that establishes the properties of inhibitory synapse function and properties of local circuitry. In this review, we will discuss how Nrxns and their ligands sculpt synaptic inhibition in a brain-region, cell-type and synapse-specific manner.

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“…Whole-cell patch-clamp recordings was performed as our previously reported [8,20] Immuno uorescence was performed according to our previous studies [8]. The mice were anesthetized with sodium pentobarbital (45 mg/kg, i.p.)…”

Section: Whole-cell Patch-clamp Recordingsmentioning

confidence: 99%

Caspase-1 modulates chronic restraint stress-induced depression and GABAergic dysfunction via regulating GAD67 in the hippocampus

Sun²,

Wang³

et al. 2022

Preprint

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Major depression disorder (MDD) is a common psychiatric disorder. Both inflammation and GABAergic dysfunction have been implicated in the pathophysiology of MDD. Caspase-1, a classic inflammatory caspase, regulates AMPARs-mediated glutamatergic neurotransmission. However, the role of caspase-1 in chronic stress-induced GABAergic dysfunction remains largely unknown. In this study, we found that serum and hippocampal caspase-1 levels increased significantly in chronic restraint stress (CRS) mice, and a significant negative correlation occurred between levels of caspase-1 and depression-like behaviors. Furthermore, CRS significantly decreased GAD67 mRNA levels and GABAARs-mediated miniature inhibitory postsynaptic currents (mIPSCs) in the hippocampus. Genetic deficiency of caspase-1 not only blocked CRS-induced depression-like behaviors, but also alleviated CRS-induced impairments in GABAergic neurotransmission, including the decreased expression of GAD67 and the amplitude and frequency of mIPSCs. Finally, reexpression of caspase-1 in the hippocampus of Caspase-1-/- mice increased susceptibility to stress-induced anxiety- and depression-like behaviors through inhibiting GAD67 expression and GABAARs-mediated mIPSCs. Our study suggests that CRS dysregulates GABAergic neurotransmission via increasing the levels of caspase-1 in the hippocampus, ultimately leading to depression-like behaviors. This work illustrates that targeting caspase-1 may provide potential therapeutic benefits to stress-related GABAergic dysfunction in the pathogenesis of MDD.

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Deficiency of Glycosylated α-Dystroglycan in Ventral Hippocampus Bridges the Destabilization of Gamma-Aminobutyric Acid Type A Receptors With the Depressive-like Behaviors of Male Mice

Cited by 14 publications

References 63 publications

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

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

Neurexins and their ligands at inhibitory synapses

Caspase-1 modulates chronic restraint stress-induced depression and GABAergic dysfunction via regulating GAD67 in the hippocampus

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