| Popis: |
BackgroundHippocampal neurogenesis dysfunction is one of the main pathogenesis of depression. Icariin (ICA) has significant anti-depression and anti-hippocampal damage effects but could not effectively cross the blood-brain-barrier and accumulate in brain. Based on the proteomics of cerebrospinal fluid (CSF), this study aimed to explore the mechanism of ICA against hippocampal neurogenesis dysfunction in depression.MethodsIn vivo, rats were exposed to 6-week CUMS and treated by ICA to observe the effects of ICA on depressive symptoms, cognitive functions, neurogenesis and number of neurons in DG. Tandem mass tag (TMT) proteomics were used to screen the differentially expressed proteins (DEPs) in CSF co-regulated by CUMS and ICA. Parallel reaction monitoring (PRM) was used to validate 10 DEPs that were related to cell proliferation and survival. In vitro, CSF was conducted on primary hippocampal neural stem cells (NSCs) to observe the proliferation and differentiation under high-corticosterone (CORT) concentration.Results It was shown that ICA could alleviate depressive symptoms, learning-memory dysfunction, neurogenesis dysfunction and neuronal loss in DG of depression rats and ICA-CSF could effectively repair the CORT-induced damage. A total of 52 DEPs co-regulated by CUMS and ICA in CSF were screened and mainly involved in ribosome pathway, PI3K-Akt pathway and IL-17 pathway. Rps4x, Rps12, Rps14, Rps19, Hsp90b1, Hsp90aa1 and HtrA1 were validated by PRM.ConclusionsThese findings indicate that to regulate the expression of proteins in CSF may be involved in the effects of ICA against hippocampal neurogenesis dysfunction in depression. |
