Ethanol withdrawal acts as an age-specific stressor to activate cerebellar p38 kinase.
Ethanol withdrawal acts as an age-specific stressor to activate cerebellar p38 kinase.
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DOI：
10.1016/j.neurobiolaging.2010.01.005
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发表时间：
2011-12
影响因子：
4.2
通讯作者：
Wen Y
中科院分区：
文献类型：
--
作者：
Jung ME;Ju X;Simpkins JW;Metzger DB;Yan LJ;Wen Y
我们研究了蛋白激酶P38是否在与反复乙醇戒断（EW）相关的脑老化变化中起作用。切除卵巢的年轻、中年和老年大鼠，有或没有17β-雌二醇（E2）植入，接受90天的乙醇重复戒断。分别用免疫组化和酶联免疫吸附试验检测小脑浦肯野神经元和全小脑裂解物中pP 38的活性表达。他们还进行了测试的旋转任务，以确定小脑神经元应激的行为表现和活性氧（ROS）和线粒体蛋白羰基，以确定氧化机制。中年EW大鼠表现出较高水平的pP 38阳性浦肯野神经元/小脑裂解物，这与增加线粒体蛋白氧化比其他饮食/年龄组相一致。由于年龄-EW组合导致的运动缺陷加重也开始于中年。相比之下，ROS含量在老年EW大鼠中达到峰值。E2处理在不同程度上减轻了每种EW效应。总的来说，pP 38可能介导与促氧化剂EW在脆弱的年龄和脆弱的神经元中的雌激素保护的方式相关的脑老化变化。
We investigated whether protein kinase P38 plays a role in the brain-aging changes associated with repeated ethanol withdrawal (EW). Ovariectomized young, middle-age and older rats, with or without 17β-estradiol (E2) implantation, received a 90-day ethanol with repeated withdrawal. They were tested for active pP38 expression in cerebellar Purkinje neurons and whole-cerebellar lysates using immunohistochemistry and enzyme-linked immunosorbent assay, respectively. They were also tested for the Rotarod task to determine the behavioral manifestation of cerebellar neuronal stress and for reactive oxygen species (ROS) and mitochondrial protein carbonyls to determine oxidative mechanisms. Middle-age EW rats showed higher levels of pP38-positive Purkinje neurons/cerebellar lysates, which coincided with increased mitochondrial protein oxidation than other diet/age groups. Exacerbated motor deficit due to age-EW combination also began at the middle age. In comparison, ROS contents peaked in older EW rats. E2 treatment mitigated each of the EW effects to a different extent. Collectively, pP38 may mediate the brain-aging changes associated with pro-oxidant EW at vulnerable ages and in vulnerable neurons in a manner protected by estrogen.
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DOI：
10.1073/pnas.0810599106
发表时间：
2009-04-21
影响因子：
11.1
作者：
Becker, Esther B. E.;Olivera, Peter L.;Davies, Kay E.
通讯作者：
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影响因子：
3.9
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DOI：
10.1124/jpet.108.146829
发表时间：
2009-03-01
影响因子：
3.5
作者：
Jung, Marianna E.;Wilson, Andrew M.;Simpkins, James W.
通讯作者：
Simpkins, James W.
影响因子：
2.9
作者：
Mausset, AL;de Seze, R;Privat, A
通讯作者：
Privat, A