Novel antidepressant effects of Paeonol alleviate neuronal injury with concomitant alterations in BDNF, Rac1 and RhoA levels in chronic unpredictable mild stress rats

摘要: Increasing evidence has suggested that major depressive disorder (MDD) is highly associated with brain-derived neurotrophic factor (BDNF) levels, dendrites atrophy, and loss of dendritic spines, especially in emotion-associated brain regions including the hippocampus. Paeonol a kind polyphenols natural product variety therapeutic effects. Recent studies have reported its antidepressant However, it unclear what signaling pathways contribute to improve MDD. The present study investigated effect on hippocampal neuronal morphology possible chronic unpredictable mild stress (CUMS) rat model. Using CUMS model, antidepressant-like was validated via depression-related behavioral tests. Neuronal CA1 DG assessed using ImageJ’s Sholl plugin RESCONSTRUCT software. BDNF pathway-related molecules determined by Western blotting. attenuated CUMS-induced depression-like behaviors, which were accompanied morphological alterations. After treatment for 4 weeks, length complexity density spines markedly increased dentate gyrus (DG). or does not selectively affect spine types. Simultaneously, administration deterred cofilin1 activation essential remolding spines. induction downregulated levels upregulated Rac1/RhoA levels; however, tendency these inhibited Paeonol. Our data suggest BDNF-Rac1/RhoA pathway may be involved attenuation damage represent novel agent depression.