Influence of heme oxygenase/carbon monoxide system on γ-aminobutyric acid B-receptor subunits in hippocampus of rats with febrile seizures

Abstract:

OBJECTIVE: Some studies have found that both heme oxygenase (HO) /carbon monoxide (CO) system and γ-aminobutyric acid B receptor subunits are involved in the pathogenesis of febrile seizure (FS). The aim of the study was to explore the effect of HO/CO system on GABA_BR subunits during FS. METHODS: Thirty-two Sprague-Dawley rats aged 21 days were randomly assigned into four groups: Control (37.0℃ water), FS, FS+hemin and FS+ZnPPⅨ groups (n=8 each). FS was induced in the last three groups by exposure to a hot water bath (45.0℃ water).Hemin(50 mg/ kg) and ZnPPⅨ(45 μmol/ kg) were intraperitoneally injected half an hour after the water bath in the FS+hemin and FS+ZnPPⅨ groups respectively. The Control and FS groups were administered with normal saline instead. The plasma level of CO was detected by the dual wavelengh spectrophotometer. The expressions of GABA_BR subunit mRNA and c-fos gene were examined by in situ hybridization. The expressions of GABA_BR subunit and Fos protein were observed by immunohistochemistry. RESULTS: The CO content in the FS group was significantly higher than that of the Control group. Hemin treatment increased the CO content while ZnPPⅨ treatment decreased the CO content.The expressions of GABA_BR_2 and GABA_BR_1 increased in the FS+hemin group compared with those in the FS group. In the FS+ZnPPⅨ group, the expression of GABA_BR_2 decreased while the GABA_BR_1 expression was not different compared with that in the FS group.Hemin treatment decreased the expression of c-fos gene and Fos protein, while ZnPPⅨ treatment elevated their expression. CONCLUSIONS: CO may play a role in the pathogenesis of FS through regulating GABA_BR function.