Epigenetic control of epilepsy target genes contributes to a cellular memory of epileptogenesis in cultured rat hippocampal neurons

Acta Neuropathologica Communications
K KieseKatja Kobow

Abstract

Hypersynchronous neuronal excitation manifests clinically as seizure (ictogenesis), and may recur spontaneously and repetitively after a variable latency period (epileptogenesis). Despite tremendous research efforts to describe molecular pathways and signatures of epileptogenesis, molecular pathomechanisms leading to chronic epilepsy remain to be clarified. We hypothesized that epigenetic modifications may form the basis for a cellular memory of epileptogenesis, and used a primary neuronal cell culture model of the rat hippocampus to study the translation of massive neuronal excitation into persisting changes of epigenetic signatures and pro-epileptogenic target gene expression. Increased spontaneous activation of cultured neurons was detected 3 and 7 days after stimulation with 10 μM glutamate when compared to sham-treated time-matched controls using calcium-imaging in vitro. Chromatin-immunoprecipitation experiments revealed short-term (3 h, 7 h, and 24 h) and long-term (3 d and 2 weeks) changes in histone modifications, which were directly linked to decreased expression of two selected epilepsy target genes, e.g. excitatory glutamate receptor genes Gria2 and Grin2a. Increased promoter methylation observed 4 weeks after gluta...Continue Reading

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Citations

Jan 30, 2020·Frontiers in Cellular Neuroscience·Karen M J van Loo, Albert J Becker
Nov 7, 2019·Epilepsy & Behavior : E&B·José Ramón BosqueDolores E López
Oct 17, 2020·European Journal of Pain : EJP·Lonnie Møller JohansenLars Arendt-Nielsen
Mar 17, 2021·Seizure : the Journal of the British Epilepsy Association·Estela M BruxelIscia Lopes-Cendes
Jun 1, 2021·Epilepsy & Behavior : E&B·Bruno Raphael Ribeiro CavalcanteRicardo Augusto Leoni De Sousa
Dec 2, 2021·American Journal of Physiology. Gastrointestinal and Liver Physiology·Yurii V StepanovTymish Y Ohulchanskyy

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Methods Mentioned

BETA
immunoprecipitation
acetylation
PCR
ChIP
fluorescence microscopy
light microscopy
histone acetylation

Software Mentioned

CLC sequence viewer
Quantitation tool for Methylation Analysis software ( RIKEN
^ F
GraphPad Prism6
GraphPad
MATLAB
Cell

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