title: Differential expression of hippocampal EphA4 and ephrinA3 in anhedonic-like behavior, stress resilience, and antidepressant drug treatment after chronic unpredicted mild stress.
abstract: Stress exposure is one of the major risk factors of depression, but the mechanism is not understood. While some individuals show resilience to stress exposure, antidepressants only partially reduce stress-induced depression in both humans and rodents. Stress could dysregulate the remodeling of neuronal dendrites and spines in hippocampus while antidepressants could recover the deficiency induced by stress. EphA4 and its ligand ephrinA3 are critical in the remodeling of neuronal dendrites and spines, but the relationship between ephrinA3/EphA4, stress-induced depression and antidepressants treatment is largely unknown. Based on a rat chronic unpredicted mild stress (CUMS) model, we investigated ephrinA3/EphA4 expression in stress susceptibility, stress resilience, treatment response and treatment resistance in rats. CUMS led to downregulation of EphA4 expression and upregulation of ephrinA3 expression in the hippocampus of stress-susceptible rats, but not in stress-resilient rats. Dysregulated EphA4 and ephrinA3 can be rescued by fluoxetine administration in drug responders, but not in fluoxetine resistant rats. These data provide insights into the potential role of EphA4 and ephrinA3 after stressor exposure, stress adaptation, fluoxetine response and drug treatment refraction.
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China; Institute of Neuropsychiatry, Wuhan University, Wuhan 430060, PR China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China; Institute of Neuropsychiatry, Wuhan University, Wuhan 430060, PR China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China; Institute of Neuropsychiatry, Wuhan University, Wuhan 430060, PR China.
authors.forename: Zhongchun
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China.
authors.forename: Qirong
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Department of Psychiatry, Renmin Hospital of Wuhan University, Jiefang Road 238#, Wuhan 430060, Hubei, PR China; Institute of Neuropsychiatry, Wuhan University, Wuhan 430060, PR China. Electronic address: gaohuawangde@163.com.
authors.forename: Gaohua
authors.initials: G
authors.lastname: Wang
mesh_terms: D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D036384:Ephrin-A3 / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017207:Rats, Sprague-Dawley; D036122:Receptor, EphA4 / Q000378:metabolism*; D013045:Species Specificity; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D000928:Antidepressive Agents; D036384:Ephrin-A3; D005473:Fluoxetine; D013395:Sucrose; D036122:Receptor, EphA4
keywords: Chronic unpredicted mild stress; Depression; EhpA4; Stress resilience; Treatment resistance; ephrinA3