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

Sci Rep. 2021 May 13;11(1):10211. doi: 10.1038/s41598-021-89534-4.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / physiology
  • Adenosine Triphosphate / metabolism
  • Animals
  • Brain / metabolism
  • Cerebrum / metabolism*
  • Cerebrum / physiology
  • Female
  • Magnetic Resonance Spectroscopy / methods
  • Mitochondrial Proton-Translocating ATPases / metabolism*
  • Oligomycins / pharmacology
  • Oxidation-Reduction
  • Oxidoreductases / metabolism
  • Pyruvate Dehydrogenase Complex / metabolism*
  • Pyruvic Acid / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tetrodotoxin / pharmacology

Substances

  • Oligomycins
  • Pyruvate Dehydrogenase Complex
  • Tetrodotoxin
  • Pyruvic Acid
  • Adenosine Triphosphate
  • Oxidoreductases
  • Mitochondrial Proton-Translocating ATPases