Neural oscillatory activity serving sensorimotor control is predicted by superoxide-sensitive mitochondrial redox environments.
Adult
Aged
Beta Rhythm
/ physiology
Female
Humans
Hydrogen Peroxide
/ metabolism
Magnetoencephalography
Male
Middle Aged
Mitochondria
/ metabolism
Models, Neurological
Movement
/ physiology
Neural Pathways
/ physiology
Oxidation-Reduction
Psychomotor Performance
/ physiology
Sensorimotor Cortex
/ physiology
Superoxides
/ metabolism
Young Adult
EPR spectroscopy
Seahorse Analyzer
magnetoencephalography
mitochondrial respiration
superoxide
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
26 10 2021
26 10 2021
Historique:
accepted:
26
07
2021
entrez:
23
10
2021
pubmed:
24
10
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
Motor control requires a coordinated ensemble of spatiotemporally precise neural oscillations across a distributed motor network, particularly in the beta range (15 to 30 Hz) to successfully plan and execute volitional actions. While substantial evidence implicates beta activity as critical to motor control, the molecular processes supporting these microcircuits and their inherent oscillatory dynamics remain poorly understood. Among these processes are mitochondrial integrity and the associated redox environments, although their direct impact on human neurophysiological function is unknown. Herein, 40 healthy adults completed a motor sequence paradigm during magnetoencephalography (MEG). MEG data were imaged in the time-frequency domain using a beamformer to evaluate beta oscillatory profiles during distinct phases of motor control (i.e., planning and execution) and subsequent behavior. To comprehensively quantify features of the mitochondrial redox environment, we used state-of-the-art systems biology approaches including Seahorse Analyzer to assess mitochondrial respiration and electron paramagnetic resonance spectroscopy to measure superoxide levels in whole blood as well as antioxidant activity assays. Using structural equation modeling, we tested the relationship between mitochondrial function and sensorimotor brain-behavior dynamics through alterations in the redox environment (e.g., generation of superoxide and alteration in antioxidant defenses). Our results indicated that superoxide-sensitive but not hydrogen peroxide-sensitive features of the redox environment had direct and mediating effects on the bioenergetic-neural pathways serving motor performance in healthy adults. Importantly, our results suggest that alterations in the redox environment may directly impact behavior above and beyond mitochondrial respiratory capacities alone and further may be effective targets for age- and disease-related declines in cognitive-motor function.
Identifiants
pubmed: 34686594
pii: 2104569118
doi: 10.1073/pnas.2104569118
pmc: PMC8639326
pii:
doi:
Substances chimiques
Superoxides
11062-77-4
Hydrogen Peroxide
BBX060AN9V
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIDA NIH HHS
ID : R01 DA047828
Pays : United States
Organisme : NINDS NIH HHS
ID : T32 NS105594
Pays : United States
Organisme : NIMH NIH HHS
ID : RF1 MH117032
Pays : United States
Organisme : NIGMS NIH HHS
ID : P30 GM103335
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH118013
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116782
Pays : United States
Informations de copyright
Copyright © 2021 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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