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首页> 外文期刊>The European Journal of Neuroscience >Overexpression of spermidine/spermine N-acetyltransferase in transgenic mice protects the animals from kainate-induced toxicity.
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Overexpression of spermidine/spermine N-acetyltransferase in transgenic mice protects the animals from kainate-induced toxicity.

机译：在转基因小鼠中亚精胺/亚精胺N-乙酰转移酶的过表达保护动物免受海藻酸盐诱导的毒性。

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We recently generated a transgenic mouse line with activated polyamine catabolism through overexpression of spermidine/spermine N1-acetyltransferase (SSAT). A detailed analysis of brain polyamine concentrations indicated that all brain regions of these animals showed distinct signs of activated polyamine catabolism, e.g. overaccumulation of putrescine (three- to 17-fold), appearance of N1-acetylspermidine and decreases in spermidine concentrations. In situ hybridization analyses revealed a marked overexpression of SSAT-specific mRNA all over the brain tissue of the transgenic animals. The transgenic animals appeared to tolerate subcutaneous injections of high-dose kainate substantially better as their overall mortality was less than 50% of that of their syngenic littermates. We used the expression of glial fibrillary acidic protein (GFAP) as a marker of brain injury in response to kainate. In situ hybridization analysis with GFAP oligonucleotide up to 7 days after the administration of sublethal kainate doses showed reduced GFAP expression in transgenic animals in comparison with their non-transgenic littermates. This difference was especially striking in the cerebral cortex of the transgenic mice where the exposure to kainate hardly induced GFAP expression. The treatment with kainate likewise resulted in loss of the hippocampal (CA3) neurons in non-transgenic but not transgenic animals. These results support our earlier findings indicating that elevated concentrations of brain putrescine, irrespective whether derived from an overexpression of ornithine decarboxylase, or as shown here, from an overexpression of SSAT, play in all likelihood a neuroprotective role in brain injury.
机译：我们最近通过过表达亚精胺/亚精胺N1-乙酰基转移酶（SSAT）生成了具有激活的多胺分解代谢的转基因小鼠品系。对脑中多胺浓度的详细分析表明，这些动物的所有大脑区域均表现出明显的活化多胺分解代谢迹象，例如腐胺的过度积累（3至17倍），N1-乙酰基亚精胺的出现和亚精胺浓度的降低。原位杂交分析表明，在整个转基因动物的脑组织中，SSAT特异性mRNA均明显过表达。转基因动物似乎对皮下注射大剂量的海藻酸盐具有更好的耐受性，因为它们的总死亡率不到同基因同窝仔的死亡率的50％。我们使用神经胶质纤维酸性蛋白（GFAP）的表达作为对红藻氨酸反应的脑损伤的标志。给予亚致死性海藻酸盐剂量后长达7天的GFAP寡核苷酸的原位杂交分析表明，与非转基因同窝仔相比，转基因动物中GFAP表达降低。这种差异在转基因小鼠的大脑皮层中尤为明显，因为暴露于海藻酸盐下几乎不会诱导GFAP表达。在非转基因动物而非转基因动物中，用海藻酸盐治疗同样导致海马（CA3）神经元的丧失。这些结果支持了我们较早的发现，表明脑腐胺的浓度升高，无论是源自鸟氨酸脱羧酶的过表达，还是来自SSAT的过表达，都很可能在脑损伤中起到神经保护作用。

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