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Exploration of the mechanism by which icariin modulates hippocampal neurogenesis in a rat model of depression
- Source :
- Neural Regeneration Research, Vol 17, Iss 3, Pp 632-642 (2022), Neural Regeneration Research
- Publication Year :
- 2022
- Publisher :
- Wolters Kluwer Medknow Publications, 2022.
-
Abstract
- Icariin (ICA) has a significant capacity to protect against depression and hippocampal injury, but it cannot effectively cross the blood-brain barrier and accumulate in the brain. Therefore, the mechanism by which ICA protects against hippocampal injury in depression remains unclear. In this study, we performed proteomics analysis of cerebrospinal fluid to investigate the mechanism by which ICA prevents dysfunctional hippocampal neurogenesis in depression. A rat model of depression was established through exposure to chronic unpredictable mild stress for 6 weeks, after which 120 mg/kg ICA was administered subcutaneously every day. The results showed that ICA alleviated depressive symptoms, learning and memory dysfunction, dysfunctional neurogenesis, and neuronal loss in the dentate gyrus of rats with depression. Neural stem cells from rat embryonic hippocampi were cultured in media containing 20% cerebrospinal fluid from each group of rats and then treated with 100 μM corticosterone. The addition of cerebrospinal fluid from rats treated with ICA largely prevented the corticosterone-mediated inhibition of neuronal proliferation and differentiation. Fifty-two differentially expressed proteins regulated by chronic unpredictable mild stress and ICA were identified through proteomics analysis of cerebrospinal fluid. These proteins were mainly involved in the ribosome, PI3K-Akt signaling, and interleukin-17 signaling pathways. Parallel reaction monitoring mass spectrometry showed that Rps4x, Rps12, Rps14, Rps19, Hsp90b1, and Hsp90aa1 were up-regulated by chronic unpredictable mild stress and down-regulated by ICA. In contrast, HtrA1 was down-regulated by chronic unpredictable mild stress and up-regulated by ICA. These findings suggest that ICA can prevent depression and dysfunctional hippocampal neurogenesis through regulating the expression of certain proteins found in the cerebrospinal fluid. The study was approved by the Experimental Animal Ethics Committee of Guangzhou University of Chinese Medicine of China in March 2017.
- Subjects :
- medicine.medical_specialty
hippocampus
icariin
dysfunctional hippocampal neurogenesis
Hippocampal formation
cerebrospinal fluid
chemistry.chemical_compound
Cerebrospinal fluid
proteomics
Developmental Neuroscience
Corticosterone
Internal medicine
medicine
Hippocampus (mythology)
RC346-429
business.industry
Dentate gyrus
Neurogenesis
Neural stem cell
chronic unpredictable mild stress
depression
ribosome pathway
Endocrinology
chemistry
Neurology. Diseases of the nervous system
business
Icariin
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 16735374
- Volume :
- 17
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Neural Regeneration Research
- Accession number :
- edsair.doi.dedup.....5de4669c38947531ec23024a076acb80