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1000
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Abstract/Summary
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Dysfunctional autophagy and impairment of adult hippocampal neurogenesis (AHN) each contribute to the
pathogenesis of major depressive disorder (MDD). However, whether dysfunctional autophagy is linked to aberrant
AHN underlying MDD remains unclear. Here we demonstrate that the expression of nuclear receptor binding factor 2
(NRBF2), a component of autophagy-associated PIK3C3/VPS34-containing phosphatidylinositol 3-kinase complex, is
attenuated in the dentate gyrus (DG) under chronic stress. NRBF2 deficiency inhibits the activity of the VPS34 complex
and impairs autophagic flux in adult neural stem cells (aNSCs). Moreover, loss of NRBF2 disrupts the neurogenesisrelated protein network and causes exhaustion of aNSC pool, leading to the depression-like phenotype. Strikingly,
overexpressing NRBF2 in aNSCs of the DG is sufficient to rescue impaired AHN and depression-like phenotype of mice.
Our findings reveal a significant role of NRBF2-dependent autophagy in preventing chronic stress-induced AHN
impairment and suggest the therapeutic potential of targeting NRBF2 in MDD treatment.
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