• Kylie Foutch, Iris Tilton, Aundrea Cooney, Cole Bender, Collin Licharz, Megan Baldemor, Caitlyn Rock, Atehsa Asal Sahagun, Robert Brock, Chloe Franzia, Mary Francis Garcia, Raghav Gupta, Christopher Arellano Reyes, Mariyam Lokhandwala, Daniela Moura, Hirofumi Noguchi, and Laura Cocas.
• 500 El Camino Real, Santa Clara University, Biology Department, Santa Clara, CA, United States.
• Neuroscience. 2025 Jan 9; 564: 144159144-159.

AbstractOligodendrocyte progenitor cells differentiate into oligodendrocytes, which myelinate axons during development and following demyelinating injury. However, the mechanisms that drive the timing and specificity of developmental myelination are not well understood. We hypothesized that oligodendrocyte progenitor cell proliferation and differentiation would be affected by pathological neuronal activity during adolescent development when developmental myelination is occurring and that this would also impact neuron-to-oligodendrocyte progenitor cell connectivity and myelination. We used kainic acid to induce a seizure in mice, treating equal numbers of males and females, in sample sizes of at least five animals. We found that the seizures led to increased cell death overall, specifically in the oligodendrocyte-lineage cells. We found that both oligodendrocyte progenitor cell proliferation and overall numbers increased, and the number of mature oligodendrocytes decreased. We found a decrease in myelin in the cerebral cortex, corpus callosum, and hippocampus after a seizure. We observed an increase in demyelinating lesions, but no change in neuronal process length, in brains after seizure, suggesting that the demyelination was due primarily to the loss of both oligodendrocyte-lineage cells. We found that Kir4.1 potassium channel expression on oligodendrocyte progenitor cells decreased after seizure, but not mature oligodendrocytes. Finally, we found a decrease in neuron-to-oligodendrocyte progenitor cell connections in seizure mice compared to controls. These findings provide insight into the response of the adolescent brain to seizure activity, as well as how seizures affect oligodendrocyte development, neuronal-glial connections, and myelin formation.Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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