Host: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
Name : WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
Location : Kyoto
Date : July 01, 2018 - July 06, 2018
Background
The Yi-nao-jie-yu Prescription (YNJYP) is an herbal prescription widely used in traditional Chinese medicine and has been recently used as a therapeutic agent for post-stroke depression (PSD). Adult neurogenesis gains significant attention as a potential cause of neurological and psychiatric disorders. The Notch signals play an important role in neurogenesis process. This study investigated the effects of YNJYP on adult neurogenesis, and explored its mechanism at the molecular level.
Method
PSD model was established by middle cerebral artery occlusion (MCAO) accompanied by chronic immobilization stress for 1 week. Sham, stroke, and PSD groups were gavaged with saline, while treatment groups received Fluoxetine hydrochloride capsules (FXT) or YNJYP. At 2, 4, and 8 weeks, depression-like behavior was evaluated by a forced swim test and sucrose consumption test. Neurogenesis was observed by double immunofluorescence staining. Notch signals (Notch1, Jagged1, Hes1, and Hes5 mRNA) were detected by real-time polymerase chain reaction.
Result
YNJYP ameliorated depression-like behavior in the forced swim test and sucrose consumption test at 2, 4, and 8 weeks. PSD decreased the differentiation toward neurons of newly born cells in the hippocampal dentate gyrus, and increased the differentiation toward astrocytes, effects that were reversed by FXT and YNJYP. At 2 weeks, compared to the stroke group, the expression of Hes5 mRNA in the PSD group decreased, but increased after treatment with FXT or YNJYP. At 4 weeks, compared to the stroke group, the expression of Notch1 and Hes1 mRNA in the PSD group decreased, but also increased after treatment with FXT or YNJYP. At 8 weeks, the expression of Notch1, Jagged1, Hes1, and Hes5 mRNA in the PSD group was higher than that in the stroke group, and remained at a high level even after treatment with FXT or YNJYP.
Conclusion
The current investigation indicated that neurogenesis is a potential mechanism for treatment of PSD, and YNJYP has a positive effect on neurogenesis by dynamically regulating the expression of Notch signaling genes.
