Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy

Version 1 : Received: 22 October 2021 / Approved: 27 October 2021 / Online: 27 October 2021 (13:36:04 CEST)

How to cite: Cho, C.; Zeigler, M.; Mizuno, S.; Morrison, R.S.; Totah, R.; Barker-Haliski, M. Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy. Preprints 2021, 2021100415 (doi: 10.20944/preprints202110.0415.v1). Cho, C.; Zeigler, M.; Mizuno, S.; Morrison, R.S.; Totah, R.; Barker-Haliski, M. Reductions in Hydrogen Sulfide Precede Onset of Mitochondrial Quality Control in the Corneal Kindled Mouse Model of Epilepsy. Preprints 2021, 2021100415 (doi: 10.20944/preprints202110.0415.v1).

Abstract

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H2S), a gasotransmitter, promotes mitochondrial function and biogenesis, elicits neuromodulation and neuroprotection, and may acutely suppress seizures. A major gap in knowledge remains in understanding the role of mitochondrial dysfunction and progressive changes in H2S levels following acute seizures and during epileptogenesis. We thus sought to quantify changes in H2S and its methylated metabolite (MeSH) via LC-MS/MS subsequent to acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the corneal kindled mouse model of chronic seizures. Plasma H2S was acutely reduced after a maximal electroshock seizure. H2S or MeSH levels in whole brain homogenate and expression of related genes in corneal kindled mice were not altered. However, plasma H2S and MeSH levels were significantly lower during kindling, but not after established kindling. Morever, we demonstrated a time-dependent increase in expression of mitochondrial membrane integrity-related proteins, Opa1, Mfn2, Drp1, and Mff during kindling, which did not correlate with gene expression. Taken together, short-term reductions in plasma H2S could be a novel biomarker for seizures. Future studies should further define the role of H2S and mitochondrial stress in epilepsy.

Keywords

epilepsy; hydrogen sulfide; corneal kindled mice, mitochondrial dysfunction, oxidative stress, LC-MS/MS; temporal lobe epilepsy; neurological disorder; gasotransmitter

Subject

MEDICINE & PHARMACOLOGY, Behavioral Neuroscience

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