Tanshinone IIA ameliorates chronic unpredictable mild stress-induced depression-like behavior and cognitive impairment in rats through the BDNF/TrkB/GAT1 signaling pathway.
Eur J Pharmacol
; 938: 175385, 2023 Jan 05.
Article
em En
| MEDLINE
| ID: mdl-36379259
ABSTRACT
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 depression-like 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 gamma-aminobutyric 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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Fator Neurotrófico Derivado do Encéfalo
/
Disfunção Cognitiva
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article