Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.

Mitochondrial Ca(2+) uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca(2+) uptake capacit...

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Autores principales: Basavaraju G Sanganahalli, Peter Herman, Fahmeed Hyder, Sridhar S Kannurpatti
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Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/66bdd89cf2934528a709af5462926dc7
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spelling oai:doaj.org-article:66bdd89cf2934528a709af5462926dc72021-11-18T07:47:10ZMitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.1932-620310.1371/journal.pone.0063317https://doaj.org/article/66bdd89cf2934528a709af5462926dc72013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23650561/?tool=EBIhttps://doaj.org/toc/1932-6203Mitochondrial Ca(2+) uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca(2+) uptake capacities on intrinsic brain activity using clinically relevant markers. From a multi-compartment estimate of probable baseline Ca(2+) ranges in the brain, we hypothesized that reduced or enhanced mitochondrial Ca(2+) uptake capacity would decrease or increase spontaneous neuronal activity respectively. As resting state fMRI-BOLD fluctuations and stimulus-evoked BOLD responses have similar physiological origins [1] and stimulus-evoked neuronal and hemodynamic responses are modulated by mitochondrial Ca(2+) uptake capacity [2], [3] respectively, we tested our hypothesis by measuring hemodynamic fluctuations and spontaneous neuronal activities during normal and altered mitochondrial functional states. Mitochondrial Ca(2+) uptake capacity was perturbed by pharmacologically inhibiting or enhancing the mitochondrial Ca(2+) uniporter (mCU) activity. Neuronal electrical activity and cerebral blood flow (CBF) fluctuations were measured simultaneously and integrated with fMRI-BOLD fluctuations at 11.7T. mCU inhibition reduced spontaneous neuronal activity and the resting state functional connectivity (RSFC), whereas mCU enhancement increased spontaneous neuronal activity but reduced RSFC. We conclude that increased or decreased mitochondrial Ca(2+) uptake capacities lead to diminished resting state modes of brain functional connectivity.Basavaraju G SanganahalliPeter HermanFahmeed HyderSridhar S KannurpattiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e63317 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Basavaraju G Sanganahalli
Peter Herman
Fahmeed Hyder
Sridhar S Kannurpatti
Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
description Mitochondrial Ca(2+) uptake, central to neural metabolism and function, is diminished in aging whereas enhanced after acute/sub-acute traumatic brain injury. To develop relevant translational models for these neuropathologies, we determined the impact of perturbed mitochondrial Ca(2+) uptake capacities on intrinsic brain activity using clinically relevant markers. From a multi-compartment estimate of probable baseline Ca(2+) ranges in the brain, we hypothesized that reduced or enhanced mitochondrial Ca(2+) uptake capacity would decrease or increase spontaneous neuronal activity respectively. As resting state fMRI-BOLD fluctuations and stimulus-evoked BOLD responses have similar physiological origins [1] and stimulus-evoked neuronal and hemodynamic responses are modulated by mitochondrial Ca(2+) uptake capacity [2], [3] respectively, we tested our hypothesis by measuring hemodynamic fluctuations and spontaneous neuronal activities during normal and altered mitochondrial functional states. Mitochondrial Ca(2+) uptake capacity was perturbed by pharmacologically inhibiting or enhancing the mitochondrial Ca(2+) uniporter (mCU) activity. Neuronal electrical activity and cerebral blood flow (CBF) fluctuations were measured simultaneously and integrated with fMRI-BOLD fluctuations at 11.7T. mCU inhibition reduced spontaneous neuronal activity and the resting state functional connectivity (RSFC), whereas mCU enhancement increased spontaneous neuronal activity but reduced RSFC. We conclude that increased or decreased mitochondrial Ca(2+) uptake capacities lead to diminished resting state modes of brain functional connectivity.
format article
author Basavaraju G Sanganahalli
Peter Herman
Fahmeed Hyder
Sridhar S Kannurpatti
author_facet Basavaraju G Sanganahalli
Peter Herman
Fahmeed Hyder
Sridhar S Kannurpatti
author_sort Basavaraju G Sanganahalli
title Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
title_short Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
title_full Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
title_fullStr Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
title_full_unstemmed Mitochondrial functional state impacts spontaneous neocortical activity and resting state FMRI.
title_sort mitochondrial functional state impacts spontaneous neocortical activity and resting state fmri.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/66bdd89cf2934528a709af5462926dc7
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AT peterherman mitochondrialfunctionalstateimpactsspontaneousneocorticalactivityandrestingstatefmri
AT fahmeedhyder mitochondrialfunctionalstateimpactsspontaneousneocorticalactivityandrestingstatefmri
AT sridharskannurpatti mitochondrialfunctionalstateimpactsspontaneousneocorticalactivityandrestingstatefmri
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