Bigio Benedetta, Sagi Yotam, Barnhill Olivia, Dobbin Josh, El Shahawy Omar, de Angelis Paolo, Nasca Carla
Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States.
Center for Dementia Research, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States.
Front Mol Neurosci. 2023 Jul 25;16:1183184. doi: 10.3389/fnmol.2023.1183184. eCollection 2023.
This invited article ad memoriam of Bruce McEwen discusses emerging epigenetic mechanisms underlying the from adverse childhood experiences to adult physiology and brain functions. The conceptual framework that we pursue suggest multidimensional biological pathways for the rapid regulation of neuroplasticity that utilize rapid non-genomic mechanisms of epigenetic programming of gene expression and modulation of metabolic function via mitochondrial metabolism. The current article also highlights how applying computational tools can foster the translation of basic neuroscience discoveries for the development of novel treatment models for mental illnesses, such as depression to slow the clinical manifestation of Alzheimer's disease. Citing an expression that many of us heard from Bruce, while "It is not possible to roll back the clock," deeper understanding of the biological pathways and mechanisms through which stress produces a lifelong vulnerability to altered mitochondrial metabolism can provide a path for compensatory neuroplasticity. The newest findings emerging from this mechanistic framework are among the latest topics we had the good fortune to discuss with Bruce the day before his sudden illness when walking to a restaurant in a surprisingly warm evening that preluded the snowstorm on December 18th, 2019. With this article, we wish to celebrate Bruce's untouched love for Neuroscience.
这篇纪念布鲁斯·麦克尤恩的特邀文章探讨了从童年不良经历到成人生理和脑功能背后新出现的表观遗传机制。我们所追求的概念框架提出了用于快速调节神经可塑性的多维生物学途径，这些途径利用基因表达的快速非基因组表观遗传编程机制以及通过线粒体代谢对代谢功能进行调节。当前文章还强调了应用计算工具如何促进基础神经科学发现的转化，以开发针对精神疾病（如抑郁症）的新型治疗模型，从而延缓阿尔茨海默病的临床表现。引用我们许多人从布鲁斯那里听到的一句话，虽然“时光无法倒流”，但深入了解压力导致线粒体代谢改变从而产生终身易感性的生物学途径和机制，可以为代偿性神经可塑性提供一条途径。从这个机制框架中涌现出的最新发现是我们有幸在2019年12月18日暴风雪前夕那个出奇温暖的夜晚，在布鲁斯突然生病前一天去餐馆的路上与他讨论的最新话题之一。通过这篇文章，我们希望颂扬布鲁斯对神经科学未曾改变的热爱。
