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

Grieb, Benjamin; Uppala, Sivaranjan; Sapir, Gal; Shaul, David; Gomori, J. Moshe; Katz-Brull, Rachel

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.

ACTION potentials; ADENOSINE triphosphate; PYRUVATE dehydrogenase kinase; BRAIN metabolism; LABORATORY rats

Scientific Reports, 2021, Vol 11, Issue 1, p1

2045-2322

Academic Journal

10.1038/s41598-021-89534-4