Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices

Abstract Direct and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action p...

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Autores principales:	Benjamin Grieb, Sivaranjan Uppala, Gal Sapir, David Shaul, J. Moshe Gomori, Rachel Katz-Brull
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/553e466a64294384a92db7eaa8530929
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spelling	oai:doaj.org-article:553e466a64294384a92db7eaa85309292021-12-02T16:50:32ZCurbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices10.1038/s41598-021-89534-42045-2322https://doaj.org/article/553e466a64294384a92db7eaa85309292021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-89534-4https://doaj.org/toc/2045-2322Abstract Direct and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.Benjamin GriebSivaranjan UppalaGal SapirDavid ShaulJ. Moshe GomoriRachel Katz-BrullNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Benjamin Grieb Sivaranjan Uppala Gal Sapir David Shaul J. Moshe Gomori Rachel Katz-Brull Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
description	Abstract Direct and real-time monitoring of cerebral metabolism exploiting the drastic increase in sensitivity of hyperpolarized 13C-labeled metabolites holds the potential to report on neural activity via in-cell metabolic indicators. Here, we followed the metabolic consequences of curbing action potential generation and ATP-synthase in rat cerebrum slices, induced by tetrodotoxin and oligomycin, respectively. The results suggest that pyruvate dehydrogenase (PDH) activity in the cerebrum is 4.4-fold higher when neuronal firing is unperturbed. The PDH activity was 7.4-fold reduced in the presence of oligomycin, and served as a pharmacological control for testing the ability to determine changes to PDH activity in viable cerebrum slices. These findings may open a path towards utilization of PDH activity, observed by magnetic resonance of hyperpolarized 13C-labeled pyruvate, as a reporter of neural activity.
format	article
author	Benjamin Grieb Sivaranjan Uppala Gal Sapir David Shaul J. Moshe Gomori Rachel Katz-Brull
author_facet	Benjamin Grieb Sivaranjan Uppala Gal Sapir David Shaul J. Moshe Gomori Rachel Katz-Brull
author_sort	Benjamin Grieb
title	Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
title_short	Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
title_full	Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
title_fullStr	Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
title_full_unstemmed	Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
title_sort	curbing action potential generation or atp-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/553e466a64294384a92db7eaa8530929
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Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slices

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