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...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2021-05-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-89534-4 |
| _version_ | 1831771165310320640 |
|---|---|
| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-22T07:53:12Z |
| format | Article |
| id | doaj.art-553e466a64294384a92db7eaa8530929 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-22T07:53:12Z |
| publishDate | 2021-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-553e466a64294384a92db7eaa85309292022-12-21T18:33:25ZengNature PortfolioScientific Reports2045-23222021-05-0111111210.1038/s41598-021-89534-4Curbing action potential generation or ATP-synthase leads to a decrease in in-cell pyruvate dehydrogenase activity in rat cerebrum slicesBenjamin Grieb0Sivaranjan Uppala1Gal Sapir2David Shaul3J. Moshe Gomori4Rachel Katz-Brull5Department of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemDepartment of Radiology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of JerusalemAbstract 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.https://doi.org/10.1038/s41598-021-89534-4 |
| spellingShingle | 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 Scientific Reports |
| title | 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_short | 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 |
| url | https://doi.org/10.1038/s41598-021-89534-4 |
| work_keys_str_mv | AT benjamingrieb curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices AT sivaranjanuppala curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices AT galsapir curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices AT davidshaul curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices AT jmoshegomori curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices AT rachelkatzbrull curbingactionpotentialgenerationoratpsynthaseleadstoadecreaseinincellpyruvatedehydrogenaseactivityinratcerebrumslices |