Neuronal and Behavioral Consequences of Early-life Seizures
Abstract number :
1.007
Submission category :
1. Basic Mechanisms / 1A. Epileptogenesis of acquired epilepsies
Year :
2023
Submission ID :
392
Source :
www.aesnet.org
Presentation date :
12/2/2023 12:00:00 AM
Published date :
Authors :
Presenting Author: Sydney Townsend, BS – The Ohio State University
Jesse Westfall, MS – Nationwide Children's Hospital; Amanda Ringland, BS – Nationwide Children's Hospital; Sahib Sran, MS – Nationwide Children's Hospital; Tracy Bedrosian, Ph.D. – Nationwide Children's Hospital
Rationale:
One in 150 children is diagnosed with epilepsy each year. Early-life seizures have profound consequences for brain development and function later in life that cause 25-50% of these patients to exhibit intellectual disability and deficits in communication, cognition, and behavior. Therefore, it is a critical need to understand how early-life seizures are affecting the trajectory of brain development. We hypothesize that uncontrolled early-life seizures cause lasting changes in chromatin accessibility and gene expression that ultimately affect brain function and behavior.
Methods:
Here we aim to correlate early-life seizures with a comprehensive set of behavioral, transcriptional, and epigenetic outcomes in mice. We developed an early-life seizure model in CD-1 mice by treating with Pentylenetetrazol (PTZ), a GABA-A receptor antagonist, that induces seizure activity. Mice were exposed to either Saline or PTZ to induce repeated seizures during a critical window of hippocampal development. We tested the behavioral consequences of early-life seizures beginning at one month of age using a suite of assays that test for cognitive and social behaviors. We performed single-cell multiomic analysis to identify transcriptional and epigenetic signatures of early-life seizures by assaying both gene expression and chromatin accessibility at multiple timepoints.
Results:
Preliminary results suggest that repeated early-life seizures cause behavioral deficits and changes in gene expression on a cell-type-specific basis, particularly in excitatory neurons.
Conclusions:
Together, these findings will elucidate the association between early-life seizures and neuronal/behavioral consequences, which may inform the connection between epilepsy and its long-term consequences.
Funding: N/A
Basic Mechanisms