Ahil/hap1-complex Involved In The Occurrence Of Depressive-like Behavior

Objects: To observe the change of Ahi1/Hap1-complex in the depressive mice andto explore the possible pathogenesis of depressive phenotype.Methods ICR mice were randomly divided into two groups: control (Con) groupand the experimental (Stress) group. Chronic restraint stress was used to establishmouse model of depression. Behavioral experiments (including forced swimming testand tail suspension test) were used to examine depressive phenotype in mice. Thecontents of neurotransmitters including serotonin (5-HT) and dopamine (DA) weremeasured by high performance liquid chromatography (HPLC). The contents ofbrain-derived neurotrophic factor (BDNF) and cortisol in brain tissue and serum weremeasured by an enzyme linked immunosorbent assay method (ELISA). Western blotanalysis was used to determine the expression of Ahi1and Hap1in different brainregions. The reverse transcription polymerase chain reaction (RT-PCR) was used tomeasure the expression levels of Ahi1mRNA.In order to study whether Ahi1and Hap1as a target of antidepressant action,mice were randomly divided into four groups, Con+saline (NS) group, Con+imipramine (IM) group, Stress+NS group, and Stress+IM group. At week, themice in the Stress group were exposured to chronic restraint stress. From the secondweek IM groups were given intraperitoneal injection of IM (20mg/kg body weight). NSgroups were given intraperitoneal injection of the same dose of saline. After three weektreatment, the changes of behaviors were evaluated by forced swimming test and tailsuspension test. The changes of the expression levels of Ahi1and Hap1were examinedby western blot.Results Tail suspension test and forced swimming test showed that the immobilitytime of Stress group were significantly increased compared with the Con group(P<0.05). The contents of5-HT and DA were significantly lower (P<0.05). The levels of BDNF in brain tissue and serum of Stress group decreased significantly (P<0.05).Serum cortisol levels of Stress group were significantly increased (P<0.05). Theexpression of Ahi1and Hap1in different brain regions were reduced in the stress group.The longer the mice were exposed to chronic restraint stress; the lower was theexpression of Ahi1and Hap1. The expression levels of Ahi1mRNA in Stress group hadno significant change compared with Con group (P>0.05). The immobility time of TSTand FST in Stress+IM group were significantly shorter than the Stress+NS group (P<0.05). In sucrose preference test, the percentage of consumed sucrose water weremarkedly decreased in Stress+NS group compared with Stress+IM group (P＜0.05).The expression levels of Ahi1and Hap1in Stress+IM group were significantly higherthan Stress+NS group (P<0.05). There was no significant difference between Stress+IM group and Con group ((P>0.05).Conclusion The expression of Ahi1and Hap1in the brain tissue of depressive-likephenotype mice were reduced; antidepressant treatment reversed the reduction of Ahi1and Hap1, suggesting that Ahi1and Hap1may have a regulatory role in thepathogenesis of depression-like behavior. Therefore，Ahi1and Hap1may be a potentialtarget for the development of antidepressants.