Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice.
Genetic and Pharmacological Manipulations of Glyoxalase 1 Mediate Ethanol Withdrawal Seizure Susceptibility in Mice.
复制标题
DOI：
10.3390/brainsci11010127
复制
发表时间：
2021-01-19
期刊：
影响因子：
3.3
通讯作者：
Palmer AA
中科院分区：
文献类型：
--
作者：
Barkley-Levenson AM;Lee A;Palmer AA
中枢神经系统（CNS）兴奋过度是急性乙醇戒断的临床显著特征。有证据表明戒断严重程度的遗传贡献，但尚未确定具体的遗传风险因素。基因glycoproteinase 1（Glo 1）先前已被牵连在小鼠的乙醇消耗中，并且Glo 1抑制可以减弱小鼠和大鼠的饮酒。在这里，我们调查是否遗传和药理学操作的GLO 1活性也可以介导乙醇戒断癫痫发作的严重程度在小鼠中。对来自两个在不同遗传背景下过表达Glo 1的转基因品系（C57 BL/6 J（B6）和FVB/NJ（FVB））的小鼠进行了处理诱导惊厥（HIC）试验，作为急性乙醇戒断的指标。注射4 g/kg酒精后，与野生型同窝小鼠相比，过表达Glo 1的B6和FVB小鼠的HIC均增加，但仅FVB系显示出统计学显著差异。我们还对野生型B6小鼠每天注射乙醇（2 g/kg + 9 mg/kg 4-甲基吡唑）10天，并在用载体或GLO 1抑制剂（S-溴苄基谷胱甘肽环戊基二酯（pBBG））处理后的第10天测试它们的HIC。用pBBG治疗减少了HIC，尽管这种效果仅在两个10天的乙醇暴露和戒断周期后才具有统计学显著性。这些结果提供了聚集的遗传学和药理学证据，GLO 1可以介导乙醇戒断癫痫易感性。
Central nervous system (CNS) hyperexcitability is a clinically significant feature of acute ethanol withdrawal. There is evidence for a genetic contribution to withdrawal severity, but specific genetic risk factors have not been identified. The gene glyoxalase 1 (Glo1) has been previously implicated in ethanol consumption in mice, and GLO1 inhibition can attenuate drinking in mice and rats. Here, we investigated whether genetic and pharmacological manipulations of GLO1 activity can also mediate ethanol withdrawal seizure severity in mice. Mice from two transgenic lines overexpressing Glo1 on different genetic backgrounds (C57BL/6J (B6) and FVB/NJ (FVB)) were tested for handling-induced convulsions (HICs) as a measure of acute ethanol withdrawal. Following an injection of 4 g/kg alcohol, both B6 and FVB mice overexpressing Glo1 showed increases in HICs compared to wild-type littermates, though only the FVB line showed a statistically significant difference. We also administered daily ethanol injections (2 g/kg + 9 mg/kg 4-methylpyrazole) to wild-type B6 mice for 10 days and tested them for HICs on the 10th day following treatment with either a vehicle or a GLO1 inhibitor (S-bromobenzylglutathione cyclopentyl diester (pBBG)). Treatment with pBBG reduced HICs, although this effect was only statistically significant following two 10-day cycles of ethanol exposure and withdrawal. These results provide converging genetic and pharmacological evidence that GLO1 can mediate ethanol withdrawal seizure susceptibility.
登录
查看更多内容
影响因子：
13.5
作者：
Breese, George R.;Sinha, Rajita;Heilig, Markus
通讯作者：
Heilig, Markus
影响因子：
3.3
作者：
Gorin-Meyer, R. E.;Wiren, K. M.;Finn, D. A.
通讯作者：
Finn, D. A.
DOI：
10.1111/j.1530-0277.2007.00509.x
发表时间：
2007-11-01
影响因子：
3.2
作者：
Gililland, Katherine R.;Finn, Deborah A.
通讯作者：
Finn, Deborah A.
影响因子：
2.9
作者：
CRABBE, JC;MERRILL, CD;BELKNAP, JK
通讯作者：
BELKNAP, JK
影响因子：
7.6
作者：
Huang, Ming-Chyi;Schwandt, Melanie L.;Heilig, Markus
通讯作者：
Heilig, Markus