Delayed Expression of Both GABABR1 and GABABR2 Subunits in Murine Hippocampal Dentate Gyrus After a Single Systemic Injection of Trimethyltin
Delayed Expression of Both GABABR1 and GABABR2 Subunits in Murine Hippocampal Dentate Gyrus After a Single Systemic Injection of Trimethyltin
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DOI：
10.1007/s11064-022-03652-7
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发表时间：
2022-06-23
影响因子：
4.4
通讯作者：
Kuramoto，Nobuyuki
中科院分区：
文献类型：
--
作者：
Onishi，Yuki;Yamamura，Yusuke;Kuramoto，Nobuyuki
三甲基锡（Trimethyltin，TMT）被用作哺乳动物海马神经元而非胶质细胞的细胞毒素。TMT全身给药导致小鼠海马齿状回（DG）和CA 3区ZnAF-2 DA染色荧光下降（作为完整苔藓纤维的标记）和Fluoro-Jade B染色荧光增加（作为退化神经元的标记），在给药后的最初2至5天内，随后在30天内有所改善。在免疫印迹分析中，GABABR 1和GABABR 2亚基水平在TMT后沿着增加，而海马DG的谷氨酸能GluA 1和GluA 2/3受体亚基水平在TMT后2 - 7天显著降低，但在其他海马区域如CA 1和CA 3区域则没有。免疫组化分析显示，GABABR 2亚基的组成型和诱导型表达的细胞免疫反应的星形胶质细胞标记，以及神经元标记的DG与GABABR 1a也GABABR 1b亚基的细胞阳性星形胶质细胞标记的情况下。这些结果表明，GABABR 1和GABABR 2亚基可能是上调的细胞以外的神经元和星形胶质细胞的DG在TMT中毒的后期阶段在小鼠。
Trimethyltin (TMT) has been used as a cytotoxin to neurons rather than glial cells in the mammalian hippocampus. The systemic administration of TMT led to declined fluorescence of ZnAF-2 DA staining as a marker of intact mossy fibers and increased fluorescence of Fluoro-Jade B staining as a marker of degenerated neurons during the initial 2 to 5 days after the administration with later ameliorations within 30 days in the hippocampal dentate gyrus (DG) and CA3 region in mice. On immunoblotting analysis, both GABABR1 and GABABR2 subunit levels increased during 15 to 30 days after TMT along with significant decreases in glutamatergic GluA1 and GluA2/3 receptor subunit levels during 2 to 7 days in the DG, but not in other hippocampal regions such as CA1 and CA3 regions. Immunohistochemical analysis revealed the constitutive and inducible expression of GABABR2 subunit in cells immunoreactive to an astrocytic marker as well as neuronal markers in the DG with the absence of neither GABABR1a nor GABABR1b subunit from cells positive to an astrocytic marker. These results suggest that both GABABR1 and GABABR2 subunits may be up-regulated in cells other than neurons and astroglia in the DG at a late stage of TMT intoxication in mice.