Hasegawa Hiroshi, Tanaka Toshiya, Kondo Mari, Teramoto Koji, Nakayama Kei, Hwang Gi-Wook
Laboratory of Hygienic Sciences, Kobe Pharmaceutical University, 4-19-1 Motoyamakita-Machi, Higashinada-Ku, Kobe, 6588558 Japan.
Laboratory of Environmental and Health Sciences, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-Ku, Sendai, Miyagi 9818558 Japan.
Toxicol Res. 2022 Dec 21;39(1):169-177. doi: 10.1007/s43188-022-00164-y. eCollection 2023 Jan.
Ethanol is toxic to the brain and causes various neurological disorders. Although ethanol can directly exert toxicity on neurons, it also acts on other cell types in the central nervous system. Blood vessel endothelial cells interact with, and are affected by blood ethanol. However, the effects of ethanol on the vascular structures of the brain have not been well documented. In this study, we examined the effects of binge levels of ethanol on brain vasculature. Immunostaining analysis indicated structural alterations of blood vessels in the cerebral cortex, which became more tortuous than those in the control mice after ethanol administration. The interaction between the blood vessels and astrocytes decreased, especially in the upper layers of the cerebral cortex. Messenger RNA expression analysis revealed a unique downregulation of mRNA encoding vascular endothelial growth factor (VEGF)-A among VEGF, angiopoietin, endothelin family angiogenic and blood vessel remodeling factors. The expression of three proteoglycan core proteins, glypican-5, neurocan, and serglycin, was also altered after ethanol administration. Thus, binge levels of ethanol affect the expression of VEGF-A and blood vessel-supporting proteoglycans, resulting in changes in the vascular structure of the cerebral cortex.
The online version contains supplementary material available at 10.1007/s43188-022-00164-y.
乙醇对大脑有毒性,并会引发各种神经紊乱。尽管乙醇可直接对神经元产生毒性作用,但它也作用于中枢神经系统中的其他细胞类型。血管内皮细胞与血液中的乙醇相互作用并受其影响。然而,乙醇对大脑血管结构的影响尚未得到充分记录。在本研究中,我们检测了暴饮水平的乙醇对脑血管系统的影响。免疫染色分析表明,大脑皮层血管结构发生改变,乙醇给药后血管比对照小鼠的血管更加扭曲。血管与星形胶质细胞之间的相互作用减少,尤其是在大脑皮层的上层。信使核糖核酸表达分析显示,在血管内皮生长因子(VEGF)、血管生成素、内皮素家族血管生成和血管重塑因子中,编码VEGF-A的信使核糖核酸出现独特的下调。乙醇给药后,三种蛋白聚糖核心蛋白(磷脂酰肌醇蛋白聚糖-5、神经蛋白聚糖和丝甘蛋白聚糖)的表达也发生了改变。因此,暴饮水平的乙醇会影响VEGF-A和支持血管的蛋白聚糖的表达,从而导致大脑皮层血管结构发生变化。
在线版本包含可在10.1007/s43188-022-00164-y获取的补充材料。