Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA; Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA; Center for Addiction Research, University of Texas Medical Branch, Galveston, TX 77555, USA.
Department of Neuroscience, Cell Biology and Anatomy, University of Texas Medical Branch, Galveston, TX 77555, USA; Center for Addiction Research, University of Texas Medical Branch, Galveston, TX 77555, USA.
Brain Res. 2019 Nov 15;1723:146425. doi: 10.1016/j.brainres.2019.146425. Epub 2019 Aug 29.
Cocaine and ethanol are two commonly co-abused substances; however, the neuropathology following chronic dual consumption is poorly understood. Neural stem cells (NSCs) are a subpopulation of cells within the adult brain that are integral to brain maintenance and repair making them an appealing target to reverse neurodegeneration associated with abused substances. Yet, knowledge about NSC response to chronic poly-drug administration of ethanol and cocaine is minimal. Here, we developed a novel chronic poly-drug administration paradigm of ethanol and cocaine using a transgenic mouse model to trace endogenous NSC survival and differentiation in three brain regions from both male and female mice. We report significant and distinct patterns of NSC survival and differentiation among brain regions, as well as between sexes. Additionally, poly-drug administration had synergistic effects on NSC survival. Altered cognitive and hedonic behaviors were also observed, however the extent of these behavioral changes was not proportional to the NSC changes. With this mouse model we can effectively examine cognitive and behavioral changes and correlate them with pathological changes in the brain in response to chronic poly-drug administration, which is of great value in understanding the progression of neurodegeneration in polysubstance use disorders and evaluation potential therapeutics on neuroregeneration.
可卡因和乙醇是两种常见的共同滥用物质；然而，慢性双重消费后的神经病理学仍知之甚少。神经干细胞（NSCs）是成年大脑中的一个细胞亚群，对大脑的维持和修复至关重要，因此成为逆转与滥用物质相关的神经退行性变的有吸引力的靶点。然而，关于 NSC 对乙醇和可卡因慢性多药物给药的反应的知识还很有限。在这里，我们使用转基因小鼠模型开发了一种新的乙醇和可卡因慢性多药物给药范例，以追踪来自雄性和雌性小鼠的三个脑区中内源性 NSC 的存活和分化。我们报告了脑区之间以及性别之间 NSC 存活和分化的显著且不同的模式。此外，多药物给药对 NSC 存活具有协同作用。还观察到认知和享乐行为的改变，但这些行为变化的程度与 NSC 变化不成比例。使用这种小鼠模型，我们可以有效地检查认知和行为变化，并将其与慢性多药物给药后大脑的病理变化相关联，这对于理解多物质使用障碍中神经退行性变的进展以及评估神经再生的潜在治疗方法具有重要价值。
