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Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype

Journal Article


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.

UOW Authors


  •   Han, Mei (external author)

Publication Date


  • 2017

Citation


  • Zhang, J. C., Yao, W., Qu, Y., Nakamura, M., Dong, C., Yang, C., . . . Hashimoto, K. (2017). Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype. Scientific Reports, 7(1). doi:10.1038/s41598-017-07325-2

Scopus Eid


  • 2-s2.0-85026733940

Web Of Science Accession Number


Volume


  • 7

Issue


  • 1

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.

UOW Authors


  •   Han, Mei (external author)

Publication Date


  • 2017

Citation


  • Zhang, J. C., Yao, W., Qu, Y., Nakamura, M., Dong, C., Yang, C., . . . Hashimoto, K. (2017). Increased EphA4-ephexin1 signaling in the medial prefrontal cortex plays a role in depression-like phenotype. Scientific Reports, 7(1). doi:10.1038/s41598-017-07325-2

Scopus Eid


  • 2-s2.0-85026733940

Web Of Science Accession Number


Volume


  • 7

Issue


  • 1