Changes of neuregulin 1 receptor ErbB4 and their significance in FMR1 gene knockout mouse

Abstract

Objective To study the expression changes of neuregulin 1 (NRGI) receptor ErbB4 in the cortex and hippocampus of fragile X mental retardation 1 (FMR1) gene knockout (KO) mice, and explore the role of ErbB4 in epilepsy susceptibility in fragile X syndrome (FXS). Methods Two weeks old male FMR1 KO mice (n=3), 4 weeks old FMR1 KO mice (n=3) and 2 weeks old male wild type (WT) mice (n=3), 4 weeks old WT mice (n=3) were chosen in our study. Immunohistochemical staining and Western blotting were performed to detect the ErbB4 positive neurons and protein expression in the cerebral cortex and hippocampus of each group. Double-labeling immunofluorescence and laser confocal microscope were used to observe the ErbB4 protein expression in the parvalbumin (PV) inter-neurons of cortex and hippocampus. Results As compared with those in the 2 and 4 weeks old WT mice, the number of ErbB4 positive neurons was significantly smaller and ErbB4 protein expressions in the cerebral cortex and hippocampus of 2 and 4 weeks old KO mice were significantly decreased (P<0.05). The number of PV and ErbB4 co-expression neurons in cortex and CA1 and CA3 hippocampus of 2 and 4 weeks old KO mice was significantly smaller than that in the 2 and 4 weeks old WT mice (P< 0.05). Conclusion The decreased ErbB4 expression is related to the decreased number of PV positive inter-neurons in the FMR1 KO mice, which is involved in the pathogenesis of FXS epilepsy susceptibility. Key words: Fragile X syndrome; ErbB4; Inter-neuron; Parvalbumin; Epilepsy