A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.
A sex difference in oxidative stress and behavioral suppression induced by ethanol withdrawal in rats.
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DOI：
10.1016/j.bbr.2016.07.054
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Metzger, Daniel B.
中科院分区：
文献类型：
--
作者：
Jung, Marianna E.;Metzger, Daniel B.
乙醇戒断（EW）是指突然终止长期大量饮酒，并引起氧化性脑损伤。在这里，我们研究了是否雌性大鼠的小脑和海马受促氧化剂EW的影响小于雄性大鼠，由于17 β-雌二醇（E2）的抗氧化作用。雌性和雄性大鼠接受为期四周的乙醇饮食，每个周期停药三周，共两个周期。将一些雌性大鼠用E2或抗氧化剂（维生素E + Co-Q10）治疗进行卵巢切除。测量小脑（Rotarod）和海马（水迷宫）相关的行为，氧化标志物（O2·−，丙二醛，蛋白质羰基），线粒体膜肿胀，和一个关键的线粒体酶，细胞色素c氧化酶（CcO）。单独地，HT22（海马）细胞经受乙醇暴露和撤回两个循环以评估CcO抑制剂对E2保护线粒体呼吸和细胞活力的作用。与雄性大鼠相比，乙醇戒断的雌性大鼠小脑和海马中的氧化标记物增加较小，E2治疗降低了氧化标记物。与雄性大鼠相比，乙醇戒断的雌性大鼠表现出更好的旋转棒，但水迷宫性能较差，伴随着更严重的线粒体膜肿胀和CcO抑制在海马。E2或抗氧化剂治疗改善了旋转棒，但没有水迷宫的表现。在CcO抑制剂的存在下，E2治疗未能保护线粒体呼吸和细胞活力从EW。这些数据表明，抗氧化剂E2有助于较小的氧化应激乙醇撤回女性比男性大鼠。他们还表明，EW诱导的海马体严重线粒体损伤可能会削弱E2对海马体相关行为的抗氧化保护作用。
Ethanol withdrawal (EW) is referred to the abrupt termination of long-term heavy drinking, and provokes oxidative brain damage. Here, we investigated whether the cerebellum and hippocampus of female rats are less affected by prooxidant EW than male rats due to the antioxidant effect of 17β-estradiol (E2). Female and male rats received a four-week ethanol diet and three-week withdrawal per cycle for two cycles. Some female rats were ovariectomized with E2 or antioxidant (Vitamin E+Co-Q10) treatment. Measurements were cerebellum (Rotarod) and hippocampus (water-maze)-related behaviors, oxidative markers (O2•−, malondialdehyde, protein carbonyls), mitochondrial membrane swelling, and a key mitochondrial enzyme, cytochrome c oxidase (CcO). Separately, HT22 (hippocampal) cells were subjected to ethanol-exposure and withdrawal for two cycles to assess the effect of a CcO inhibitor on E2’s protection for mitochondrial respiration and cell viability. Ethanol-withdrawn female rats showed a smaller increase in oxidative markers in cerebellum and hippocampus than male rats, and E2 treatment decreased the oxidative markers. Compared to male counterparts, ethanol-withdrawn female rats showed better Rotarod but poorer water-maze performance, accompanied by more severe mitochondrial membrane swelling and CcO suppression in hippocampus. E2 or antioxidant treatment improved Rotarod but not water-maze performance. In the presence of a CcO inhibitor, E2 treatment failed to protect mitochondrial respiration and cell viability from EW. These data suggest that antioxidant E2 contributes to smaller oxidative stress in ethanol-withdrawn female than male rats. They also suggest that EW-induced severe mitochondrial damage in hippocampus may blunt E2’s antioxidant protection for hippocampus-related behavior.
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DOI：
10.1124/jpet.106.107896
发表时间：
2007-01-01
影响因子：
3.5
作者：
Alele, P. E.;Devaud, L. L.
通讯作者：
Devaud, L. L.
影响因子：
2.3
作者：
Gonzaga, Natalia A.;Mecawi, Andre S.;Tirapelli, Carlos R.
通讯作者：
Tirapelli, Carlos R.
影响因子：
10.6
作者：
BROWN, ME;ANTON, RF;BALLENGER, JC
通讯作者：
BALLENGER, JC
影响因子：
7.9
作者：
Bowers JM;Waddell J;McCarthy MM
通讯作者：
McCarthy MM
DOI：
10.1016/j.bbadis.2009.09.007
发表时间：
2010-01-01
影响因子：
6.2
作者：
Borras, Consuelo;Gambini, Juan;Vina, Jose
通讯作者：
Vina, Jose