PDGF-BB-Dependent Neurogenesis Buffers Depressive-Like Behaviors by Inhibition of GABAergic Projection from Medial Septum to Dentate Gyrus.
Adv Sci (Weinh)
; 10(22): e2301110, 2023 08.
Article
in En
| MEDLINE
| ID: mdl-37325895
ABSTRACT
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 (PDGFRß) in NSCs blocks an increase in NSCs proliferation and the antidepressant effects of PDGF-BB. These results delineate a previously unidentified PDGF-BB/PDGFRß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Neurogenesis
/
Gamma-Aminobutyric Acid
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Adv Sci (Weinh)
Year:
2023
Document type:
Article
Affiliation country:
China