Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.
Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.
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DOI：
10.1038/s41598-018-20424-y
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发表时间：
2018-02-02
影响因子：
4.6
通讯作者：
Nedergaard M
中科院分区：
文献类型：
--
作者：
Lundgaard I;Wang W;Eberhardt A;Vinitsky HS;Reeves BC;Peng S;Lou N;Hussain R;Nedergaard M
已知长期摄入过量乙醇对中枢神经系统（CNS）有不良影响。在这里，我们研究了急性和慢性乙醇暴露以及从慢性乙醇暴露中戒断对胶质淋巴功能的影响，胶质淋巴功能是一个与外周淋巴系统相连的全脑代谢物清除系统。急性和慢性暴露于1.5 g/kg（狂欢水平）乙醇显着抑制清醒小鼠的胶质淋巴功能。慢性暴露于1.5 g/kg乙醇增加GFAP的表达和诱导的星形胶质细胞特异性水通道水通道蛋白4（AQP 4）的错位，但降低了几种细胞因子的水平。令人惊讶的是，在急性暴露后以及慢性暴露一个月后，用0.5 g/kg（低剂量）乙醇处理的小鼠的胶质淋巴功能增加。低剂量的慢性乙醇摄入与GFAP表达的显著降低相关，与生理盐水组相比，细胞因子谱几乎没有变化。这些观察结果表明，乙醇对胶质淋巴系统具有J形效应，由此低剂量的乙醇增加胶质淋巴功能。相反，长期摄入1.5 g/kg乙醇可诱导反应性神经胶质增生和胶质淋巴功能紊乱，这可能导致重度饮酒者患痴呆症的风险更高。
Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, glymphatic function increased in mice treated with 0.5 g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group. These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic 1.5 g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.
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DOI：
10.3233/jpd-150533
发表时间：
2015
期刊：
Journal of Parkinson's disease
影响因子：
--
作者：
Bettiol SS;Rose TC;Hughes CJ;Smith LA
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青少年暴饮暴食改变了小鼠的成人脑神经递质的表达，行为，大脑区域体积和神经化学。
DOI：
10.1111/j.1530-0277.2010.01385.x
发表时间：
2011-04
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Coleman LG Jr;He J;Lee J;Styner M;Crews FT
通讯作者：
Crews FT
DOI：
10.4049/jimmunol.1003049
发表时间：
2011-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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作者：
Goswami R;Kaplan MH
通讯作者：
Kaplan MH
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
DOI：
10.1111/j.1530-0277.2011.01576.x
发表时间：
2011-12
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Fortier CB;Leritz EC;Salat DH;Venne JR;Maksimovskiy AL;Williams V;Milberg WP;McGlinchey RE
通讯作者：
McGlinchey RE