Abstract:
We have recently shown delayed increases in GABAB receptor (GABABR) subunit protein levels in the hippocampal dentate gyrus (DG), but not in the pyramidal CA1 and CA3 regions, at 15-30 days after the systemic single administration of trimethyltin (TMT) in mice. An attempt was thus made to determine whether the delayed increases return to the control levels found in naive mice afterward. In the DG on hippocampal slices obtained at 90 days after the administration, however, marked increases were still seen in protein levels of both GABABR1 and GABABR2 subunits without significant changes in calbindin and glial fibrillary acidic protein (GFAP) levels on immunoblotting analysis. Fluoro-Jade B staining clearly revealed the absence of degenerated neurons from the DG at 90 days after the administration. Although co-localization was invariably detected between GABABR2 subunit and GFAP in the DG at 30 days on immunohistochemical analysis, GABABR2-positive cells did not merge well with GFAP-positive cells in the DG at 90 days. These results suggest that both GABABR1 and GABABR2 subunits would be tardily and sustainably up-regulated by cells other than neurons and astrocytes in the murine DG at 90 days after a systemic single injection of TMT.
摘要:
我们最近显示了海马齿状回(DG)中GABAB受体(GABABR)亚基蛋白水平的延迟增加,但不是在锥体CA1和CA3区域,在小鼠全身单次施用三甲基锡(TMT)后15-30天。因此试图确定延迟的增加是否返回到之后在幼稚小鼠中发现的对照水平。在给药后90天获得的海马切片上的DG,然而,在免疫印迹分析中,GABABR1和GABABR2亚基的蛋白质水平仍然显着增加,而钙结合蛋白和神经胶质原纤维酸性蛋白(GFAP)水平没有显着变化。Fluoro-JadeB染色清楚地显示在给药后90天,DG中不存在退化的神经元。尽管在免疫组织化学分析30天时在DG中的GABABR2亚基和GFAP之间总是检测到共定位,在90天时,GABABR2阳性细胞未与DG中的GFAP阳性细胞良好合并。这些结果表明,在全身单次注射TMT后90天,小鼠DG中除神经元和星形胶质细胞以外的细胞将缓慢且持续地上调GABABR1和GABABR2亚基。