Role of the GABA-A system in estrogen-induced protection against brain lipid peroxidation in ethanol-withdrawn rats.
Role of the GABA-A system in estrogen-induced protection against brain lipid peroxidation in ethanol-withdrawn rats.
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GABA-A 系统在雌激素诱导的乙醇戒断大鼠脑脂质过氧化保护中的作用。
DOI：
10.1097/01.alc.0000148100.78628.e7
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Simpkins,JamesW
中科院分区：
文献类型：
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作者：
Rewal,Mridula;Jung,MariannaE;Simpkins,JamesW
背景：我们先前的研究表明，17 β-雌二醇（E2）治疗可部分通过GABA能系统保护乙醇戒断大鼠的小脑神经元死亡和相关运动缺陷。在这项研究中，我们研究了GABA-A拮抗剂荷包牡丹碱对E2的神经保护作用的影响，通过评估氧化标记硫代巴比妥酸反应物质（TBARS）在乙醇戒断（EW.Methods）：卵巢切除的动物植入E2（EW/E2）或油（EW/Oil）丸接受液体乙醇（7.5%w/v）或糊精7天，通过管饲法。从EW发作前3天开始，给予GABA-A拮抗剂荷包牡丹碱（1.25 mg/kg）（每天3次，腹腔内），持续4天。在EW 7小时时检测明显的EW体征后，立即处死一组动物，收集小脑、海马和皮质。进一步处理脑匀浆用于TBARS测定，以在存在或不存在FeCl 3的情况下检测TBARS。为了评估运动能力，另一组动物进行了测试的潜伏期下降1周后，从旋转棒EW。结果：EW/油动物增强了内源性和FeCl 3刺激的TBARS水平在小脑和海马的方式增强荷包牡丹碱，但抑制E2。当荷包牡丹碱与E2一起沿着给药时，可抵消E2的保护作用。Pearson相关系数表明，从旋转杆下降的潜伏期与TBARS水平在小脑和hippocamps.Conclusion：这些数据表明，E2保护乙醇戒断大鼠的脆弱脑区的脂质过氧化，部分通过GABA能系统。
Background:Our previous study showed that 17 β‐estradiol (E2) treatment protects against cerebellar neuronal death and related motor deficits in ethanol‐withdrawn rats, in part through the GABAergic system. In this study, we examined the effect of the GABA‐A antagonist bicuculline on the neuroprotective effect of E2 by assessing the oxidative marker thiobarbituric acid reactive substances (TBARS) during ethanol withdrawal (EW).Methods:Ovariectomized animals that had implants of E2 (EW/E2) or oil (EW/Oil) pellets received liquid ethanol (7.5% w/v) or dextrin for 7 days by gavage. The GABA‐A antagonist bicuculline (1.25 mg/kg) was administered (three times a day intraperitoneally) for 4 days starting 3 days before the onset of EW. After testing for overt EW signs at 7 hr of EW, one set of the animals was immediately killed for the collection of the cerebellum, hippocampus, and cortex. The brain homogenates were further processed for TBARS assay to detect TBARS in the presence or absence of FeCl3. For assessing motor capacity, the other set of animals was tested for the latency to fall from a rotarod after 1 week of EW.Results:The EW/Oil animals had enhanced endogenous and FeCl3‐stimulated TBARS levels in the cerebellum and the hippocampus in a manner potentiated by bicuculline but inhibited by E2. Bicuculline counteracted the protective effect of E2 when administered along with E2. Pearson correlation coefficients indicated that the latency to fall from the rotarod covaried with TBARS levels in the cerebellum and the hippocampus.Conclusion:These data suggest that E2 protects against lipid peroxidation in vulnerable brain areas of ethanol‐withdrawn rats, in part through the GABAergic system.