Expression Of GABA_A Receptor α1 And δ Subunits In Cortex And Hippocampus Of Fragile X Syndrome

Objective:To observe the expression of theα1 andδsubunits of GABAA receptors in the neurons of cortex and hippocampus of the fragile X mouse model, FMR1 gene knockout mice, for the seek of relationship between neurophysiologic consequences of GABAA receptors and the phenotype of fragile X syndrome, and prospect a novel therapeutic target for treatment of the fragile X phenotype. Methods: Immunohistochemistry was used, calculated the integrated optical density (IOD) of the positive neurons as the expression level of the targeted protein, analyzed and compared the difference of expression of GABAA receptorα1 andδsubunits between FMR1 gene knockout mice(KO)and wild-type control littermates(WT). Results:GABAA receptorα1 andδsubunits showed in cytoplasm of the neurons in parietal cortex and hippocampus. Compared to WT group, the expression of GABAA receptor al subunit protein in KO mice decreased significantly in cortex and hippocampus (P<.05). We confirmed nearly 37.6%reduction in expression ofα1 subunit in cortex and 57%in hippocampus. Moreover, decreased expression of theδsubunit also found in KO mice in both cortex and hippocampus (P<0.05), nearly 35.4%under expression in cortex and 33.8%in hippocampus. Conclusions:Both the GABAA receptorsal and 8 subunits are significantly under expressed in the cortex and hippocampus of FMR1 knockout mice. The under expression ofα1 andδsubunits may contribute to the behavioral abnormalities and epilepsy in the fragile X syndrome.