Laboratorio de función y patología neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile; Centro de Investigación y Estudio del Consumo de Alcohol en Adolescentes (CIAA), Santiago, Chile.
Laboratorio de función y patología neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Biochem Biophys Res Commun. 2020 Jul 30;528(3):514-519. doi: 10.1016/j.bbrc.2020.05.160. Epub 2020 Jun 4.
Binge drinking is the consumption of large volumes of alcohol in short periods and exerts its effects on the central nervous system, including the hippocampus. We have previously shown that binge drinking alters mitochondrial dynamics and induces neuroinflammation in the hippocampus of adolescent rats. Mild traumatic brain injury (mTBI), is regularly linked to alcohol consumption and share mechanisms of brain damage. In this context, we hypothesized that adolescent binge drinking could prime the development of brain damage generated by mTBI. We found that alcohol binge drinking induced by the "drinking in the dark" (DID) paradigm increases oxidative damage and astrocyte activation in the hippocampus of adolescent mice. Interestingly, adolescent animals submitted to DID showed decreased levels of mitofusin 2 that controls mitochondrial dynamics. When mTBI was evaluated as a second challenge, hippocampi from animals previously submitted to DID showed a reduction in dendritic spine number and a different spine profile. Mitochondrial performance could be compromised by alterations in mitochondrial fission in DID-mTBI animals. These data suggest that adolescent alcohol consumption can modify the progression of mTBI pathophysiology. We propose that mitochondrial impairment and oxidative damage could act as priming factors, modifying predisposition against mTBI effects.
binge drinking 是指在短时间内大量饮酒,对中枢神经系统产生影响,包括海马体。我们之前的研究表明 binge drinking 会改变线粒体的动态,并在青少年大鼠的海马体中引发神经炎症。轻度创伤性脑损伤 (mTBI) 通常与饮酒有关,且具有共同的脑损伤机制。在此背景下,我们假设青少年 binge drinking 可能会引发由 mTBI 引起的脑损伤。我们发现,通过“黑暗饮酒” (DID) 范式诱导的酒精 binge drinking 会增加青少年小鼠海马体中的氧化损伤和星形胶质细胞激活。有趣的是,接受 DID 的青少年动物表现出控制线粒体动态的线粒体融合蛋白 2 水平降低。当评估 mTBI 作为第二次挑战时,先前接受 DID 的动物的海马体显示树突棘数量减少和不同的棘突形态。在 DID-mTBI 动物中,线粒体裂变的改变可能会使线粒体功能受损。这些数据表明,青少年饮酒会改变 mTBI 病理生理学的进展。我们提出,线粒体损伤和氧化损伤可能作为启动因素,改变对 mTBI 效应的易感性。