Epigenetic embedding of childhood adversity: mitochondrial metabolism and neurobiology of stress-related CNS diseases

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Omar El Shahawy¹  Benedetta Bigio²  Yotam Sagi³  Carla Nasca⁴  Paolo de Angelis⁵  Josh Dobbin⁵  Olivia Barnhill⁵ 

[1] Department of Population Health, New York University Grossman School of Medicine, New York, NY, United States;Department of Psychiatry, New York University Grossman School of Medicine, New York, NY, United States;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;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;Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY, United States;Department of Neuroscience and Physiology, New York University Grossman School of Medicine, New York, NY, United States;Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, NY, United States;

关键词: hippocampus;    acetyl-L-carnitine;    glutamate;    histone;    mood disorders;    depression;    cognition;    opioid use disorders;   

DOI  :  10.3389/fnmol.2023.1183184

 received in 2023-03-09, accepted in 2023-04-21,  发布年份 2023

来源: Frontiers

【 摘 要 】

This invited article ad memoriam of Bruce McEwen discusses emerging epigenetic mechanisms underlying the long and winding road 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.

【 授权许可】

Unknown   
Copyright © 2023 Bigio, Sagi, Barnhill, Dobbin, El Shahawy, de Angelis and Nasca.