Reductions in Hydrogen Sulfide and Changes in Mitochondrial Quality Control Proteins Are Evident in the Early Phases of the Corneally Kindled Mouse Model of Epilepsy

• Published in: International journal of molecular sciences Vol. 23; no. 3; p. 1434
• Main Authors: Cho, Christi, Zeigler, Maxwell, Mizuno, Stephanie, Morrison, Richard S, Totah, Rheem A, Barker-Haliski, Melissa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 27-01-2022; MDPI
• Subjects: Animals; Apoptosis; Brain; Chromatography, Liquid; Convulsions & seizures; Cornea; corneally kindled mice; Disease; Disease Models, Animal; Electroconvulsive therapy; Electroshock - adverse effects; Epilepsy; Epilepsy - etiology; Epilepsy - metabolism; Gene expression; Gene Expression Regulation; Hydrogen sulfide; Hydrogen Sulfide - blood; Ischemia; Kindling; Kindling, Neurologic; LC-MS/MS; Male; Metabolism; Metabolites; Methylated metabolites; Methylation; Mice; Mitochondria; Mitochondria - metabolism; mitochondrial dysfunction; Mitochondrial Proteins - metabolism; Neurodegeneration; Neuromodulation; Neuroprotection; Oxidative stress; Plasma; Proteins; Quality control; Seizures; Tandem Mass Spectrometry; Time Factors; corneally kindled mice; epilepsy; LC-MS/MS; temporal lobe epilepsy; hydrogen sulfide; gasotransmitter; mitochondrial dysfunction; oxidative stress; neurological disorder
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms23031434

Epilepsy is a heterogenous neurological disorder characterized by recurrent unprovoked seizures, mitochondrial stress, and neurodegeneration. Hydrogen sulfide (H
S) is a gasotransmitter that 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 H
S levels following acute seizures or during epileptogenesis. We thus sought to quantify changes in H
S and its methylated metabolite (MeSH) via LC-MS/MS following acute maximal electroshock and 6 Hz 44 mA seizures in mice, as well as in the early phases of the corneally kindled mouse model of chronic seizures. Plasma H
S was acutely reduced after a maximal electroshock seizure. H
S or MeSH levels and expressions of related genes in whole brain homogenates from corneally kindled mice were not altered. However, plasma H
S levels were significantly lower during kindling, but not after established kindling. Moreover, 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 changes in gene expression. Taken together, short-term reductions in plasma H
S could be a novel biomarker for seizures. Future studies should further define the role of H
S and mitochondrial stress in epilepsy.