Psychosocial experiences are associated with human brain mitochondrial biology

• 成果类型: Article
• 署名作者: Trumpff, Caroline; Monzel, Anna S.; Sandi, Carmen; Menon, Vilas; Klein, Hans - Ulrich; Fujita, Masashi; Lee, Annie; Petyuk, Vladislav A.; Hurst, Cheyenne; Duong, Duc M.; Seyfried, Nicholas T.; Wingo, Aliza P.; Wingo, Thomas S.; Wang, Yanling; Thambisetty, Madhav; Ferrucci, Luigi; Bennett, David A.; Jager, Philip L. De; Picard, Martin
• 署名单位: Columbia University; NewYork-Presbyterian Hospital; Swiss Federal Institutes of Technology Domain; Ecole Polytechnique Federale de Lausanne; NewYork-Presbyterian Hospital; Columbia University; United States Department of Energy (DOE); Pacific Northwest National Laboratory; Emory University; Emory University; Rush University; National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); National Institutes of Health (NIH) - USA; NIH National Institute on Aging (NIA); Columbia University; NewYork-Presbyterian Hospital; New York State Psychiatry Institute; Columbia University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11147
• DOI: 10.1073/pnas.2317673121
• 发表日期: 2024-07-02
• 关键词: mild cognitive impairment; alzheimers-disease; nucleus-accumbens; psychological stress; depressive behavior; social network; rush memory; mouse model; metabolism; expression

摘要

Psychosocial experiences affect brain health and aging trajectories, but the molecular pathways underlying these associations remain unclear. Normal brain function relies on energy transformation by mitochondria oxidative phosphorylation (OxPhos). Two main lines of evidence position mitochondria both as targets and drivers of psychosocial experiences. On the one hand, chronic stress exposure and mood states may alter multiple aspects of mitochondrial biology; on the other hand, functional variations in mitochondrial OxPhos capacity may alter social behavior, stress reactivity, and mood. But are psychosocial exposures and subjective experiences linked to mitochondrial biology in the human brain? By combining longitudinal antemortem assessments of psychosocial factors with postmortem brain (dorsolateral prefrontal cortex) proteomics in older adults, we find that higher well- being is linked to greater abundance of the mitochondrial OxPhos machinery, whereas higher negative mood is linked to lower OxPhos protein content. Combined, positive and negative psychosocial factors explained 18 to 25% of the variance in the abundance of OxPhos complex I, the primary biochemical entry point that energizes brain mitochondria. Moreover, interrogating mitochondrial psychobiological associations in specific neuronal and nonneuronal brain cells with for positive psychosocial experiences and mitochondria in glia but opposite associations in neurons. As a result, these mind- mitochondria associations were masked in bulk RNA- seq, highlighting the likely underestimation of true psychobiological effect sizes in bulk brain tissues. Thus, self- reported psychosocial experiences are linked to human brain mitochondrial phenotypes.