Tanshinone IIA ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment in rats through the BDNF/TrkB/GAT1 signaling pathway

Background: Depression is a common disorder with a complex pathogenesis. Tanshinone IIA (TAN IIA) is a botanical agent with neuroprotective and antidepressant properties. Objective: To examine the effects of TAN IIA on chronic unpredictable mild stress (CUMS)-induced depressionlike behavior and cognitive impairment in rats.Methods: Rats were exposed to CUMS for 4 weeks, followed by the oral administration of TAN IIA, Deanxit (DEAN), or normal saline for an additional 4 weeks. The control rats were fed with regular chow and administered with normal saline for 4 weeks. Behavioral tests were performed to assess the effects of TAN IIA on depression-like behavior and cognitive impairment in rats with CUMS. The morphology of dendrites was analyzed by Golgi staining. Immunofluorescence staining was performed to determine protein localization.Results: TAN IIA treatment ameliorated CUMS-induced depression-like behavior and cognitive impairment in rats. TAN IIA treatment also reversed the effects of CUMS on dendritic complexity and the levels of gammaaminobutyric acid (GABA) in the hippocampus and prefrontal cortex. Rats with CUMS showed decreased levels of brain-derived neurotrophic factor (BDNF) and phosphorylated tropomyosin receptor kinase B (TrkB), upregulated expression of GABA transporter 1 (GAT1), and reduced expression of synaptic proteins in the hippocampus, while TAN IIA treatment significantly diminished the effects of CUMS exposure. In addition, GAT1 was colocalized with N-methyl-D-aspartate receptor 2B.Conclusion: TAN IIA ameliorates CUMS-induced depression-like behavior and cognitive impairment in rats by regulating the BDNF/TrkB/GAT1 signaling pathway, suggesting that TAN IIA may be a candidate drug for the treatment of depression.