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雄性未成年大鼠的狂饮行为及其与小脑持续的行为损伤和促炎/促凋亡蛋白升高的关系。

Binge drinking in male adolescent rats and its relationship to persistent behavioral impairments and elevated proinflammatory/proapoptotic proteins in the cerebellum.

机构信息

School of Pharmacy, Memorial University, Health Sciences Centre, 300 Prince Philip Drive, St. John's, NL, A1B 3V6, Canada.

Department of Psychology, Memorial University, St. John's, NL, Canada.

出版信息

Psychopharmacology (Berl). 2020 May;237(5):1305-1315. doi: 10.1007/s00213-020-05458-3. Epub 2020 Jan 27.

DOI:10.1007/s00213-020-05458-3
PMID:31984446
Abstract

RATIONALE

To demonstrate that repeated episodes of binge drinking during the adolescent period can lead to long-term deficits in motor function and memory in adulthood, and increase proteins in the brain involved with inflammation and apoptotic cell death.

METHODS

Groups of early adolescent (PND 26) and periadolescent (PND 34) Sprague-Dawley rats were exposed to either ethanol or plain air through a vapor chamber apparatus for five consecutive days (2 h per day), achieving a blood ethanol concentration equivalent to 6-8 drinks in the treatment group. Subjects then underwent a series of behavioral tests designed to assess memory, anxiety regulation, and motor function. Brains were collected on PND 94 for subsequent western blot analysis.

RESULTS

Behavioral testing using the rota-rod, cage-hang, novel object recognition, light-dark box, and elevated plus maze apparatuses showed significant differences between groups; several of which persisted for up to 60 days after treatment. Western blot testing indicated elevated levels of caspase-3/cleaved caspase-3, NF-kB, and PKC/pPKC proteins in the cerebella of ethanol-treated animals.

CONCLUSIONS

Differences on anxiety tests indicate a possible failure of behavioral inhibition in the treatment group leading to riskier behavior. Binge drinking also impairs motor coordination and object memory, which involve the cerebellar and hippocampal brain regions, respectively. These experiments indicate the potential dangers of binge drinking while the brain is still developing and indicate the need for future studies in this area.

摘要

原理

为了证明青少年时期反复出现的狂饮行为会导致成年后运动功能和记忆力的长期缺陷,并增加大脑中与炎症和细胞凋亡有关的蛋白质。

方法

早期青春期(PND 26)和青春期(PND 34)的 Sprague-Dawley 大鼠被置于蒸气室装置中,通过吸入乙醇或空气 5 天(每天 2 小时),使实验组的血乙醇浓度相当于 6-8 杯酒。然后,研究对象接受了一系列旨在评估记忆、焦虑调节和运动功能的行为测试。在 PND 94 时收集大脑,用于随后的 Western blot 分析。

结果

使用转棒、笼吊、新物体识别、明暗箱和高架十字迷宫装置进行的行为测试显示了组间的显著差异;其中一些差异在治疗后持续了长达 60 天。Western blot 测试表明,乙醇处理动物的小脑中海马体中的 caspase-3/cleaved caspase-3、NF-kB 和 PKC/pPKC 蛋白水平升高。

结论

焦虑测试中的差异表明,治疗组可能存在行为抑制失败,导致更危险的行为。狂饮还会损害运动协调和物体记忆,分别涉及小脑和海马脑区。这些实验表明,在大脑仍在发育时狂饮的潜在危险,并表明该领域需要进一步研究。

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