Quercetin alleviates chronic unpredictable mild stress-induced depressive-like behaviors by promoting adult hippocampal neurogenesis via FoxG1/CREB/ BDNF signaling pathway
| Autor: | Zhong-Xuan Ma, Ru-Yi Zhang, Xia Feng, Zhi-Qing Wang, Wen-Juan Rui |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Neurogenesis Nerve Tissue Proteins CREB Hippocampus Neuroprotection Mice 03 medical and health sciences Behavioral Neuroscience chemistry.chemical_compound 0302 clinical medicine Neurotrophic factors Internal medicine medicine Animals heterocyclic compounds 030304 developmental biology Mice Inbred ICR 0303 health sciences Behavior Animal biology Depression Chemistry Brain-Derived Neurotrophic Factor Dentate gyrus Forkhead Transcription Factors CREB-Binding Protein Antidepressive Agents Neural stem cell Doublecortin Disease Models Animal Endocrinology biology.protein Quercetin Stress Psychological 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Behavioural Brain Research. 406:113245 |
| ISSN: | 0166-4328 |
| Popis: | Quercetin, a naturally occurring flavonoid, has been reported to exert antidepressant effects, however, the underlying mechanisms are still uncertain. Recent studies have demonstrated that Forkhead box transcription factor G1 (FoxG1) regulates the process of adult hippocampal neurogenesis (AHN) and exerts neuroprotective effects. In this study, we explored whether quercetin plays an anti-depressant role via regulation of FoxG1 signaling in mice and revealed the potential mechanisms. To explore the antidepressant effects of quercetin, mice were subjected to behavioral tests after a chronic unpredictable mild stress (CUMS) exposure. We found that chronic quercetin treatment (15 mg/kg, 30 mg/kg) obviously restored the weight loss of mice caused by CUMS and alleviated CUMS-induced depression-like behaviors, such as increased sucrose consumption, improved locomotor activity and shorten immobility time. In addition, to clarify the relationship between quercetin and AHN, we detected neurogenesis markers in the dentate gyrus (DG) of the hippocampus. Furthermore, FoxG1-siRNA was employed and then stimulated with quercetin to further investigate the mechanism by which FoxG1 participates in the antidepressant effects of quercetin. Our results indicate that chronic quercetin treatment dramatically increased the number of doublecortin (DCX)-positive and BrdU/NeuN-double positive cells. Besides, the expression levels of FoxG1, p-CREB and Brain-derived neurotrophic factor (BDNF) were also enhanced by quercetin in the DG. Strikingly, quercetin failed to reverse the levels of p-CREB and BDNF after FoxG1-siRNA was performed in SH-SY5Y cells and Neural Progenitor Cells (NPCs). Our results thus far suggest that quercetin might exert antidepressant effects via promotion of AHN by FoxG1/CREB/ BDNF signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect