In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice
In vivo and in vitro glycogenic effects of methionine sulfoximine are different in two inbred strains of mice
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DOI：
10.1016/s0006-8993(01)03380-7
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发表时间：
2002-03-08
期刊：
影响因子：
2.9
通讯作者：
Cloix, JF
中科院分区：
文献类型：
--
作者：
Bernard-Hélary, K;Ardourel, MY;Cloix, JF
我们研究了两种近交系小鼠品系中脑糖原合成代谢与蛋氨酸亚磺酰亚胺 (MSO) 诱导的癫痫发作之间的关系，这两种小鼠品系对惊厥具有不同的易感性。 CBA/J 被认为是 hISO 高反应菌株，C57BL/6J 被认为是 MSO 低反应菌株。因此，诱导CBA/J小鼠癫痫发作所需的MSO剂量低于C57BL/6J小鼠，并且发生癫痫发作的CBA/J小鼠在第一次惊厥期间死亡。此外，CBA/J 小鼠中 MSO 效应的时程比 C57BL/6J 小鼠中更快。在分别给予 75 mg/kg（亚惊厥剂量）和 40 mg/kg MSO（亚惊厥剂量，非致死剂量）后，对 C57BL/6J 和 CBA/J 小鼠进行分析。在惊厥前期，MSO 仅诱导 C57BL/6J 小鼠脑糖原含量增加。施用 MSO 24 小时后，两种菌株的脑糖原含量均增加。在所有实验时间点，与对照小鼠相比，MSO 处理的 C57BL/6J 小鼠中果糖 1,6-双磷酸酶（糖异生途径的最后一个关键酶）的活性和表达均有所增加，而 CBA/J 小鼠中的活性和表达在 MSO 给药后仅 24 小时有所增加。后面的结果对应于没有癫痫发作的 CBA/J 小鼠。有趣的是，体内观察到的差异与两种菌株的原代培养星形胶质细胞的结果一致。该数据表明，代谢障碍不是癫痫发作的结果，可能与两种菌株之间癫痫易感性的差异有关，具体取决于它们的遗传背景。 (C) 2002 Elsevier Science B.V. 保留所有权利。
We investigated the relationship between brain glycogen anabolism and methionine sulfoximine (MSO)-induced seizures in two inbred mouse strains that presented differential susceptibility to the convulsant. CBA/J was considered a hISO-high-reactive strain and C57BL/6J a MSO-low-reactive strain. Accordingly, the dose of MSO needed to induce seizures in CBA/J mice is lower than that in C57BL/6J mice, and CBA/J mice which had seizures, died during the first convulsion. In addition, the time-course of the MSO effect is faster in CBA/J mice than that in C57BL/6J mice. Analyses were performed in C57BL/6J and CBA/J mice after administration of 75 (subconvulsive dose) and 40 mg/kg of MSO (subconvulsive dose, not lethal dose), respectively. In the preconvulsive period, MSO induced an increase in the brain glycogen content of C57BL/6J mice only. Twenty-four hours after MSO administration, the brain glycogen content increased in both strains. The activity and expression of fructose-1,6-bisphosphatase, the last key enzyme of the gluconeogenic pathway, were increased in MSO-treated C57BL/6J mice as compared to control mice, at all experimental time points, whereas they were increased in CBA/J mice only 24 h after MSO administration. These latter results correspond to CBA/J mice that did not have seizures. Interestingly, the differences observed in vivo were consistent with results in primary cultured astrocytes from the two strains. This data suggests that the metabolism impairment, which was not a consequence of seizures, could be related to the difference in seizure susceptibility between the two strains, depending on their genetic background. (C) 2002 Elsevier Science B.V. All rights reserved.