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- W2050889194 abstract "Current antidepressant treatments remain limited by poor efficacy and a slow onset of action. Increasing evidence demonstrates that enriched environment (EE) treatment can promote structural and behavioral plasticity in the brain and dampen stress-induced alterations of neuroplasticity. Here, we have examined whether short term exposure to EE is able to produce antidepressant-like effects. Our results show that housing adult mice in an EE cage for 7 days led to antidepressant-like behavioral profiles and a significant increase in the number of dendritic spines in hippocampal CA1 pyramidal neurons. These EE-induced antidepressant-like effects are primarily attributed to increased vascular endothelial growth factor (VEGF) expression through a hypoxia-inducible factor-1α (HIF-1α)-mediated transcriptional mechanism. Blockade of HIF-1α synthesis by lentiviral infection with HIF-1α small hairpin RNAs completely blocked the increase in expression of VEGF and the antidepressant-like effects induced by EE. Moreover, no significant antidepressant-like effects were observed with EE treatment in VEGF receptor 2 (Flk-1) knock-out mice. The increase in HIF-1α expression in the hippocampus induced by EE was associated with a decrease in endogenous levels of microRNA-107 (miR-107). Overexpression of miR-107 in the hippocampus completely blocked EE-induced HIF-1α expression and the antidepressant-like effects. These results support a model in which the down-regulation of miR-107, acting through HIF-1α, mediates VEGF-dependent spinogenesis to underlie the EE-induced antidepressant-like effects." @default.
- W2050889194 created "2016-06-24" @default.
- W2050889194 creator A5018506745 @default.
- W2050889194 creator A5031754749 @default.
- W2050889194 creator A5052488836 @default.
- W2050889194 creator A5081570946 @default.
- W2050889194 date "2012-11-01" @default.
- W2050889194 modified "2023-09-26" @default.
- W2050889194 title "Vascular Endothelial Growth Factor-dependent Spinogenesis Underlies Antidepressant-like Effects of Enriched Environment" @default.
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- W2050889194 doi "https://doi.org/10.1074/jbc.m112.392076" @default.
- W2050889194 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3510798" @default.
- W2050889194 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23074224" @default.