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Published on: July 12, 2021
Expression Profiling after Prolonged Experimental Febrile Seizures in Mice Suggests Structural Remodeling in the
Bart C Jongbloets1, Koen L I van Gassen1, Anne A Kan1
1Brain Center Rudolf Magnus, Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.
Insights
Experimental febrile seizures in young mice caused structural brain changes and altered gene expression. This research sheds light on the molecular mechanisms underlying the long-term risks of febrile seizures in children.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Febrile seizures are common in young children, with complex cases increasing the risk of temporal lobe epilepsy.
- Understanding the molecular and structural changes following febrile seizures is crucial for identifying epilepsy development mechanisms.
Purpose of the Study:
- To investigate the short- and long-term structural and molecular consequences of experimental febrile seizures (eFS) in a mouse model.
- To identify candidate genes and biological processes involved in the brain's response to eFS.
Main Methods:
- Induced eFS in susceptible mice (C57BL/6J) at post-natal day 10 via hyperthermia.
- Analyzed structural hippocampal changes at 14 days post-eFS.
- Performed genome-wide transcriptome analysis (mRNA expression) from 1 hour to 56 days after eFS.
- Validated gene expression changes using in situ hybridization and histology.
Main Results:
- Detected structural re-organization in the hippocampus 14 days after eFS.
- Identified 931 differentially regulated genes following eFS.
- Observed temporal regulation of stress responses, immune and inflammatory processes, glia activation, glutamate-glutamine cycling, and myelination.
Conclusions:
- This study provides the first genome-wide transcriptome analysis of eFS in mice.
- Identified key molecular pathways and structural changes occurring after eFS, offering insights into epileptogenesis.
- Findings are vital for understanding the long-term effects of febrile seizures and developing potential therapeutic strategies.
Abstract:
Febrile seizures are the most prevalent type of seizures among children up to 5 years of age (2-4% of Western-European children). Complex febrile seizures are associated with an increased risk to develop temporal lobe epilepsy. To investigate short- and long-term effects of experimental febrile seizures (eFS), we induced eFS in highly febrile convulsion-susceptible C57BL/6J mice at post-natal day 10 by exposure to hyperthermia (HT) and compared them to normotherm-exposed (NT) mice. We detected structural re-organization in the hippocampus 14 days after eFS. To identify molecular candidates, which entrain this structural re-organization, we investigated temporal changes in mRNA expression profiles eFS 1 hour to 56 days after eFS. We identified 931 regulated genes and profiled several candidates using in situ hybridization and histology at 3 and 14 days after eFS. This is the first study to report genome-wide transcriptome analysis after eFS in mice. We identify temporal regulation of multiple processes, such as stress-, immune- and inflammatory responses, glia activation, glutamate-glutamine cycle and myelination. Identification of the short- and long-term changes after eFS is important to elucidate the mechanisms contributing to epileptogenesis.
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