CAJ | 학술논문

目的明确神经调节蛋白1 (NRG1)在Fmr1基因敲除(KO)小鼠中的变化,探讨其在脆性X综合征发病机制中的作用. 方法应用免疫组织化学染色法检测FVB近交系雄性2周龄Fmr1 KO小鼠(KO2w)、4周龄Fmr1 KO小鼠(KO4w)和同龄野生型(WT)小鼠大脑皮层及海马CA1区、CA3区、齿状回中神经调节蛋白1的阳性神经元的数量；Western blotting检测上述小鼠大脑皮层和海马组织NRG1蛋白的含量. 结果与同龄WT小鼠相比,KO2w、KO4w小鼠大脑皮层、海马CA1和CA3区NRG1阳性神经元的数量明显减少,在海马齿状回却明显增多,差异均有统计学意义(P＜0.05)；KO2w、KO4w小鼠大脑皮层、海马中NRG1含量(相对分子质量为55 000亚型)分别较同龄的WT小鼠明显减少,差异亦有统计学意义(P＜0.05). 结论 Fmr1 KO小鼠大脑皮层和海马组织NRG1阳性神经元及NRG1蛋白表达明显减少,NRG1可能参与脆性X综合征发病机制.
목적 명학신경조절단백1 (NRG1)재Fmr1기인고제(KO)소서중적변화,탐토기재취성X종합정발병궤제중적작용. 방법 응용면역조직화학염색법검측FVB근교계웅성2주령Fmr1 KO소서(KO2w)、4주령Fmr1 KO소서(KO4w)화동령야생형(WT)소서대뇌피층급해마CA1구、CA3구、치상회중신경조절단백1적양성신경원적수량；Western blotting검측상술소서대뇌피층화해마조직NRG1단백적함량. 결과 여동령WT소서상비,KO2w、KO4w소서대뇌피층、해마CA1화CA3구NRG1양성신경원적수량명현감소,재해마치상회각명현증다,차이균유통계학의의(P＜0.05)；KO2w、KO4w소서대뇌피층、해마중NRG1함량(상대분자질량위55 000아형)분별교동령적WT소서명현감소,차이역유통계학의의(P＜0.05). 결론 Fmr1 KO소서대뇌피층화해마조직NRG1양성신경원급NRG1단백표체명현감소,NRG1가능삼여취성X종합정발병궤제.
Objective To explore the expression changes ofneuregulin 1 (NRG1) in Fmr1 gene knockout (Fmr1 KO) mice,and its possible role in fragile X syndrome pathogenesis.Methods Immunohistochemistry and Western blotting were simultaneously employed to detect the expression levels of NRG 1 in the hippocampus and the cortex of FVB strain Fmr1 KO mice and wild type (WT) controls at the age of 2 and 4 weeks.Results The number of NRG1-positive cells in the CA1 and CA3 regions of hippocampus and the cortex of Fmr1 KO mice at the age of 2 and 4 weeks was significantly smaller than that in the age-matched WT mice (P＜0.05).The NRG1 protein levels in the hippocampus and cerebral cortex of Fmr1 KO mice at the age of 2 and 4 weeks were also decreased as compared with those in the age-matched WT mice (P＜0.05).Conclusion The number of NRG1-positive cells and NRG1 protein levels in the CA1 and CA3 regions of hippocampus and the cortex of Fmr1 KO mice are decreased,indicating that NRG 1 might involve in the pathogenesis of Fragile X syndrome.