Metabotropic Glutamate Receptor 5 Involved In The Regulation Of Depressive Phenotypes In Ahi1 Knockout Mice

Objective: To explore the mechanism of depressive phenotypes in Ahi1 knockout mice,and investigate whether the metabotropic glutamate receptor 5(mGluR5)involved in the regulation of depressive like behavior in Ahi knockout mice.Methods: The genotypes of Ahi1 gene were identified,and the expression of Ahi1 protein in Ahi1(-/-)mice was detected by western blot.The forced swimming test,the tail suspension test and self-grooming test were used to examine depressive phenotype in mice.Further proved,expression of p-S6 by Western blot.The mRNA level of mGluR5 in the hippocampus was detected by real-time quantitative PCR,metabolism glutamate receptor 5 inhibitor MPEP reversed depressive phenotype of Ahi1(-/-)mice.Results: Genotyping confirmed that Ahi1(-/-)mice and Ahi1(+/-)mice meet the experimental requirements.In Ahi1(-/-)mice the levels of Ahi1 protein were significantly decreased by further Western blot.Compared with Ahi1(+/-)mice,tail suspension test and forced swimming test showed that the immobility time of Ahi1(-/-)mice were significantly increased(p<0.05).Compared with Ahi1(+/-)mice,self-grooming test showed that the self grooming time of Ahi1(-/-)mice were significantly decreased(p<0.05),thus,the behavioral test indicated that Ahi1(-/-)had depressive phenotype.Further,the levels of p-S6 were significantly decreased in Ahi1(-/-)mice(p<0.05)by western blot test.The levels of mRNA mGlu R5 were significantly increased(p<0.05)in Ahi1(-/-)mice.Importantly,metabotropic glutamate receptor 5 inhibitor(MPEP)reversed the depressive phenotype of Ahi1(-/-)mice,including the immobility time in tail suspension test(p<0.05)and forced swimming test(p<0.05).Conclusion: Ahi1(-/-)mice had depressive phenotype,and the metabotropic glutamate receptor 5(mGlu R5)involved in the regulation of depressive like behavior in Ahi knockout mice.