Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch at Galveston, Galveston 77555, USA; Institute for Translational Sciences, University of Texas Medical Branch at Galveston, Galveston 77555, USA; Center for Addiction Research, University of Texas Medical Branch at Galveston, Galveston 77555, USA; Department of Neurology, Johns Hopkins, Baltimore 21287, USA.
Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch at Galveston, Galveston 77555, USA.
Stem Cell Reports. 2017 Dec 12;9(6):1916-1930. doi: 10.1016/j.stemcr.2017.10.007. Epub 2017 Nov 9.
Chronic alcohol abuse results in alcohol-related neurodegeneration, and critical gaps in our knowledge hinder therapeutic development. Neural stem cells (NSCs) are a subpopulation of cells within the adult brain that contribute to brain maintenance and recovery. While it is known that alcohol alters NSCs, little is known about how NSC response to alcohol is related to sex, brain region, and stage of differentiation. Understanding these relationships will aid in therapeutic development. Here, we used an inducible transgenic mouse model to track the stages of differentiation of adult endogenous NSCs and observed distinct NSC behaviors in three brain regions (subventricular zone, subgranular zone, and tanycyte layer) after long-term alcohol consumption. Particularly, chronic alcohol consumption profoundly affected the survival of NSCs in the subventricular zone and altered NSC differentiation in all three regions. Significant differences between male and female mice were further discovered.
慢性酒精滥用会导致与酒精相关的神经退行性变,而我们在这方面的知识空白严重阻碍了治疗方法的发展。神经干细胞(NSCs)是成年大脑中的一个细胞亚群,有助于大脑的维持和恢复。虽然已知酒精会改变 NSCs,但对于 NSC 对酒精的反应如何与性别、大脑区域和分化阶段有关,我们知之甚少。了解这些关系将有助于治疗方法的开发。在这里,我们使用可诱导的转基因小鼠模型来跟踪成年内源性 NSCs 的分化阶段,并观察到长期饮酒后三个脑区(侧脑室下区、颗粒下区和室管膜下细胞层)中 NSC 的不同行为。特别是,慢性酒精摄入会显著影响侧脑室下区 NSCs 的存活,并改变所有三个区域的 NSC 分化。还进一步发现了雄性和雌性小鼠之间的显著差异。