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PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus
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PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus
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Journal Article
PDGF‐BB‐Dependent Neurogenesis Buffers Depressive‐Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus
2023
Overview
Hippocampal circuitry stimulation is sufficient to regulate adult hippocampal neurogenesis and ameliorate depressive‐like behavior, but its underlying mechanism remains unclear. Here, it is shown that inhibition of medial septum (MS)‐dentate gyrus (DG) circuit reverses the chronic social defeat stress (CSDS)‐induced depression‐like behavior. Further analysis exhibits that inhibition of gamma‐aminobutyric acidergic neurons in MS projecting to the DG (MSGABA+‐DG) increases the expression of platelet‐derived growth factor‐BB (PDGF‐BB) in somatostatin (SOM) positive interneurons of DG, which contributes to the antidepressant‐like effects. Overexpression of the PDGF‐BB or exogenous administration of PDGF‐BB in DG rescues the effect of chronic stress on the inhibition of neural stem cells (NSCs) proliferation and dendritic growth of adult‐born hippocampal neurons, as well as on depressive‐like behaviors. Conversely, knockdown of PDGF‐BB facilitates CSDS‐induced deficit of hippocampal neurogenesis and promotes the susceptibility to chronic stress in mice. Finally, conditional knockdown platelet‐derived growth factor receptor beta (PDGFRβ) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF‐BB. These results delineate a previously unidentified PDGF‐BB/PDGFRβ signaling in regulating depressive‐like behaviors and identify a novel mechanism by which the MSGABA+‐DG pathway regulates the expression of PDGF‐BB in SOM‐positive interneurons. The study describes the functional connectivity in the MSGABA+‐DG circuit and the novel downstream molecule PDGF‐BB. Inhibition of MSGABA+‐DG pathway increases the expression of PDGF‐BB in SOM‐positive interneurons, which is capable of enhancing adult hippocampal neurogenesis in a PDGFRβ‐dependent manner by activating the Janus kinase‐signal transducer 2 and activator of transcription 3 (JAK2/STAT3) signaling pathway, leading to the improvement of chronic stress‐induced depressive‐like behavior.
Publisher
John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
Subject
