Psychosocial experiences are associated with human brain mitochondrial biology

被引:5
作者
Trumpff, Caroline [1 ]
Monzel, Anna S. [1 ]
Sandi, Carmen [2 ]
Menon, Vilas [3 ]
Klein, Hans - Ulrich [3 ]
Fujita, Masashi [3 ]
Lee, Annie
Petyuk, Vladislav A. [4 ]
Hurst, Cheyenne
Duong, Duc M. [5 ]
Seyfried, Nicholas T. [5 ]
Wingo, Aliza P. [6 ]
Wingo, Thomas S. [6 ]
Wang, Yanling [7 ]
Thambisetty, Madhav [8 ]
Ferrucci, Luigi [9 ]
Bennett, David A. [7 ]
Jager, Philip L. De
Picard, Martin [1 ,10 ,11 ,12 ]
机构
[1] Columbia Univ, Dept Psychiat, Div Behav Med, Irving Med Ctr, New York, NY 10032 USA
[2] Ecole Polytech Fed Lausanne, Brain Mind Inst, Lab Behav Genet, CH-1015 Lausanne, Switzerland
[3] Columbia Univ, Ctr Translat & Computat Neuroimmunol, Dept Neurol, Irving Med Ctr, New York, NY 10032 USA
[4] Pacific Northwest Natl Lab, Biol Sci Div, Richland, WA 99354 USA
[5] Emory Univ, Dept Biochem, Atlanta, GA 30329 USA
[6] Emory Univ, Sch Med, Dept Neurol & Human Genet, Atlanta, GA 30329 USA
[7] Rush Univ, Dept Neurol Sci, Med Ctr, Chicago, IL 60612 USA
[8] NIA, Clin & Translat Neurosci Sect, Lab Behav Neurosci, Intramural Res Program, Baltimore, MD 21224 USA
[9] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Intramural Res Program,NIH, Bethesda, MD 20892 USA
[10] Columbia Univ, H Houston Merritt Ctr, Dept Neurol, Columbia Translat Neurosci Initiat,Irving Med Ctr, New York, NY 10032 USA
[11] New York State Psychiat Inst & Hosp, Div Behav Med, New York, NY 10032 USA
[12] Columbia Univ, Robert N Butler Columbia Aging Ctr, Mailman Sch Publ Hlth, New York, NY 10032 USA
关键词
single; nucleus RNA sequencing (RNA; seq) revealed strong cell; type; specific associations; mitochondria | psychosocial factors | proteome | transcriptome | single cell RNA; seq; resolution; positive psychosocial; human brain health; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE; NUCLEUS-ACCUMBENS; PSYCHOLOGICAL STRESS; DEPRESSIVE BEHAVIOR; SOCIAL NETWORK; RUSH MEMORY; MOUSE MODEL; METABOLISM; EXPRESSION;
D O I
10.1073/pnas.2317673121
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
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.
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页数:12
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