Wang Guixiang, Wang Wenjia, Zhang Ye, Gou Xiaoying, Zhang Qingqing, Huang Yanmiao, Zhang Kuo, Zhang Haotian, Yang Jingyu, Li Yuting
Wuya College of Innovation, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China.
Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang, Liaoning Province, China.
Neural Regen Res. 2024 Feb;19(2):416-424. doi: 10.4103/1673-5374.379051.
Adolescent binge drinking leads to long-lasting disorders of the adult central nervous system, particularly aberrant hippocampal neurogenesis. In this study, we applied in vivo fluorescent tracing using NestinCreER::Rosa26-tdTomato mice and analyzed the endogenous neurogenesis lineage progression of neural stem cells (NSCs) and dendritic spine formation of newborn neurons in the subgranular zone of the dentate gyrus. We found abnormal orientation of tamoxifen-induced tdTomato (tdTom) NSCs in adult mice 2 months after treatment with EtOH (5.0 g/kg, i.p.) for 7 consecutive days. EtOH markedly inhibited tdTom NSCs activation and hippocampal neurogenesis in mouse dentate gyrus from adolescence to adulthood. EtOH (100 mM) also significantly inhibited the proliferation to 39.2% and differentiation of primary NSCs in vitro. Adult mice exposed to EtOH also exhibited marked inhibitions in dendritic spine growth and newborn neuron maturation in the dentate gyrus, which was partially reversed by voluntary running or inhibition of the mammalian target of rapamycin-enhancer of zeste homolog 2 pathway. In vivo tracing revealed that EtOH induced abnormal orientation of tdTom NSCs and spatial misposition defects of newborn neurons, thus causing the disturbance of hippocampal neurogenesis and dendritic spine remodeling in mice.
青少年暴饮会导致成人中枢神经系统出现持久紊乱，尤其是海马神经发生异常。在本研究中，我们使用NestinCreER::Rosa26-tdTomato小鼠进行体内荧光追踪，并分析了齿状回颗粒下区神经干细胞（NSCs）的内源性神经发生谱系进展以及新生神经元的树突棘形成。我们发现，在用乙醇（5.0 g/kg，腹腔注射）连续处理7天2个月后，成年小鼠中他莫昔芬诱导的tdTom（tdTom）NSCs出现异常定向。乙醇显著抑制了从青春期到成年期小鼠齿状回中tdTom NSCs的激活和海马神经发生。乙醇（100 mM）在体外也显著抑制了原代NSCs的增殖至39.2%并抑制其分化。暴露于乙醇的成年小鼠在齿状回中树突棘生长和新生神经元成熟方面也表现出明显抑制，通过自愿跑步或抑制雷帕霉素靶蛋白-增强子结合蛋白2通路可部分逆转这种抑制。体内追踪显示，乙醇诱导tdTom NSCs出现异常定向以及新生神经元的空间错位缺陷，从而导致小鼠海马神经发生和树突棘重塑受到干扰。
