Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype
Abstract Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4–ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effec...
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Nature Portfolio
2017
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oai:doaj.org-article:0f45d7fbf32c4ae391afa79a31346e942021-12-02T15:06:01ZIncreased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype10.1038/s41598-017-07325-22045-2322https://doaj.org/article/0f45d7fbf32c4ae391afa79a31346e942017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07325-2https://doaj.org/toc/2045-2322Abstract Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4–ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effect of EphA4 inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the nucleus accumbens (NAc), of susceptible mice after social defeat stress. Furthermore, the p-EphA4/EphA4 ratio was higher in the parietal cortex of depressed patients compared with controls. Systemic administration of rhynchophylline, produced a rapid antidepressant-like effect in a social defeat stress model by inhibiting EphA4–ephexin1 signaling and activating brain-derived neurotrophic factor-TrkB signaling in the PFC and hippocampus. Pretreatment with rhynchophylline before each social defeat stress could prevent the onset of the depression-like phenotype after repeated social defeat stress. Overexpression of EphA4 in the medial PFC owing to infection with an EphA4 adeno-associated virus caused the depression-like phenotype 3 weeks later and rhynchophylline had a rapid antidepressant-like effect in these mice. These findings suggest that increased EphA4–ephexin1 signaling in the PFC plays a role in the pathophysiology of depression.Ji-chun ZhangWei YaoYouge QuMayumi NakamuraChao DongChun YangQian RenMin MaMei HanYukihiko ShirayamaAkiko Hayashi-TakagiKenji HashimotoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) |
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Medicine R Science Q Ji-chun Zhang Wei Yao Youge Qu Mayumi Nakamura Chao Dong Chun Yang Qian Ren Min Ma Mei Han Yukihiko Shirayama Akiko Hayashi-Takagi Kenji Hashimoto Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| description |
Abstract Accumulating evidence suggests a role of the ephrin receptor EphA4 and the downstream protein ephexin1 in synaptic plasticity, which is implicated in depression. We examined whether EphA4–ephexin1 signaling plays a role in the pathophysiology of depression, and the antidepressant-like effect of EphA4 inhibitor rhynchophylline. We found increased ratios of p-EphA4/EphA4 and p-ephexin1/ephexin1 in the prefrontal cortex (PFC) and hippocampus but not in the nucleus accumbens (NAc), of susceptible mice after social defeat stress. Furthermore, the p-EphA4/EphA4 ratio was higher in the parietal cortex of depressed patients compared with controls. Systemic administration of rhynchophylline, produced a rapid antidepressant-like effect in a social defeat stress model by inhibiting EphA4–ephexin1 signaling and activating brain-derived neurotrophic factor-TrkB signaling in the PFC and hippocampus. Pretreatment with rhynchophylline before each social defeat stress could prevent the onset of the depression-like phenotype after repeated social defeat stress. Overexpression of EphA4 in the medial PFC owing to infection with an EphA4 adeno-associated virus caused the depression-like phenotype 3 weeks later and rhynchophylline had a rapid antidepressant-like effect in these mice. These findings suggest that increased EphA4–ephexin1 signaling in the PFC plays a role in the pathophysiology of depression. |
| format |
article |
| author |
Ji-chun Zhang Wei Yao Youge Qu Mayumi Nakamura Chao Dong Chun Yang Qian Ren Min Ma Mei Han Yukihiko Shirayama Akiko Hayashi-Takagi Kenji Hashimoto |
| author_facet |
Ji-chun Zhang Wei Yao Youge Qu Mayumi Nakamura Chao Dong Chun Yang Qian Ren Min Ma Mei Han Yukihiko Shirayama Akiko Hayashi-Takagi Kenji Hashimoto |
| author_sort |
Ji-chun Zhang |
| title |
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| title_short |
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| title_full |
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| title_fullStr |
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| title_full_unstemmed |
Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| title_sort |
increased epha4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype |
| publisher |
Nature Portfolio |
| publishDate |
2017 |
| url |
https://doaj.org/article/0f45d7fbf32c4ae391afa79a31346e94 |
| work_keys_str_mv |
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