Maladaptive myelination promotes generalized epilepsy progression

Abstract

Activity-dependent myelination can fine-tune neural network dynamics. Conversely, aberrant neuronal activity, as occurs in disorders of recurrent seizures (epilepsy), could promote maladaptive myelination, contributing to pathogenesis. In this study, we tested the hypothesis that activity-dependent myelination resulting from absence seizures, which manifest as frequent behavioral arrests with generalized electroencephalography (EEG) spike-wave discharges, promote thalamocortical network hypersynchrony and contribute to epilepsy progression. We found increased oligodendrogenesis and myelination specifically within the seizure network in two models of generalized epilepsy with absence seizures (Wag/Rij rats and Scn8a+/mut mice), evident only after epilepsy onset. Aberrant myelination was prevented by pharmacological seizure inhibition in Wag/Rij rats. Blocking activity-dependent myelination decreased seizure burden over time and reduced ictal synchrony as assessed by EEG coherence. These findings indicate that activity-dependent myelination driven by absence seizures contributes to epilepsy progression; maladaptive myelination may be pathogenic in some forms of epilepsy and other neurological diseases.

Recent advances in deciphering oligodendrocyte heterogeneity with single-cell transcriptomics

“…Unfortunately, the analysis of OLs has often not been of primary interest and therefore not explored in detail. Other CNS disorders with a recently discovered role of OLs in its disease etiology, e.g., epilepsy ( Knowles et al, 2022 ), are still awaiting in-depth single-cell transcriptomic characterization. Attention is also required for the OLs in the acute CNS injuries, where their role is largely unexplored.…”

Low-Cost Platform for Multianimal Chronic Local Field Potential Video Monitoring with Graphical User Interface (GUI) for Seizure Detection and Behavioral Scoring

“…When studying epilepsy, simultaneous monitoring of the neurophysiological signals and behavior is necessary to make meaningful connections between the observed neural activity and the subject’s behavior ( Berger, 1929 ). Many groups have developed various software packages and platforms for managing neurophysiological and video data ( Campagnola et al, 2014 ; Black et al, 2017 ; Kimchi et al, 2020 ; Knowles et al, 2022 ). Here, we aimed to develop a platform that would allow for the flexibility to perform simultaneous LFP and video monitoring, as well as high density single unit recordings which are becoming more common in epilepsy research ( Lenck-Santini and Holmes, 2008 ; Hernan et al, 2014 ; Ewell et al, 2015 , 2019 ; Dahal et al, 2019 ; Shuman et al, 2020 ).…”

Myelin plasticity in ventral tegmental area is required for opioid reward

“…Thus, which neuronal subtypes, in which circuits and with which patterns of activity elicit oligodendroglial responses remain to be fully understood. Furthermore, much remains to be learned about how activity-regulated myelination may become maladaptive and contribute to the pathophysiology of neurological ( 32 ) or psychiatric ( 33 ) diseases.…”