Adolescent seizure impacts oligodendrocyte maturation, neuronal-glial circuit Formation, and myelination in the mammalian forebrain

Neuroscience. 2025 Jan 9:564:144-159. doi: 10.1016/j.neuroscience.2024.11.050. Epub 2024 Nov 19.

Abstract

Oligodendrocyte 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.

Keywords: Myelin; Neural development; OPC; Oligodendrocyte; Seizure; Synapses.

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cell Proliferation / physiology
  • Female
  • Kainic Acid
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myelin Sheath* / metabolism
  • Myelin Sheath* / pathology
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons* / metabolism
  • Neurons* / pathology
  • Oligodendrocyte Precursor Cells / metabolism
  • Oligodendrocyte Precursor Cells / pathology
  • Oligodendrocyte Precursor Cells / physiology
  • Oligodendroglia* / metabolism
  • Oligodendroglia* / pathology
  • Prosencephalon* / pathology
  • Seizures* / metabolism
  • Seizures* / pathology

Substances

  • Kainic Acid