Regulation of Cerebral BDNF, VEGF, and GluN2B Gene Expression and Cytokine Levels by Riparin A in a Murine Model of Depression.

Abstract

Riparin A is a synthetic compound with established antidepressant and anxiolytic properties. Given its therapeutic potential and the crucial roles of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and the GluN2B subunit of the N-methyl-D-aspartate (NMDA) receptor in the pathophysiology and treatment of depression, this study aimed to evaluate the effects of Riparin A on the expression of these neurotrophic factors and receptor subunit in the hippocampus and cortex of rats subjected to the chronic unpredictable mild stress (CUMS) model of depression. Using RT-qPCR, we observed that Riparin A significantly upregulated BDNF and VEGF mRNA levels while downregulating GluN2B expression, remarkably on the hippocampal area. Furthermore, ELISA assays revealed that Riparin A modulated neuroinflammation by reducing proinflammatory cytokines TNF-α and IL-1β while increasing anti-inflammatory cytokines IL-4 and IL-10. These findings support the antidepressant properties of Riparin A and shed light on its underlying mechanisms, reinforcing the interplay between neurotrophic and inflammatory pathways in pathophysiology of depression and its treatment.