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Simultaneous Video-EEG-ECG Monitoring to Identify Neurocardiac Dysfunction in Mouse Models of Epilepsy
Published on: January 29, 2018
Different microRNA profiles in chronic epilepsy versus acute seizure mouse models
Anita Kretschmann1, Benedicte Danis, Lidija Andonovic
1Institute of Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany.
Abstract:
Epilepsy affects around 50 million people worldwide, and in about 65% of patients, the etiology of disease is unknown. MicroRNAs are small non-coding RNAs that have been suggested to play a role in the pathophysiology of epilepsy. Here, we compared microRNA expression patterns in the hippocampus using two chronic models of epilepsy characterised by recurrent spontaneous seizures (pilocarpine and self-sustained status epilepticus (SSSE)) and an acute 6-Hz seizure model. The vast majority of microRNAs deregulated in the acute model exhibited increased expression with 146 microRNAs up-regulated within 6 h after a single seizure. In contrast, in the chronic models, the number of up-regulated microRNAs was similar to the number of down-regulated microRNAs. Three microRNAs-miR-142-5p, miR-331-3p and miR-30a-5p-were commonly deregulated in all three models. However, there is a clear overlap of differentially expressed microRNAs within the chronic models with 36 and 15 microRNAs co-regulated at 24 h and at 28 days following status epilepticus, respectively. Pathway analysis revealed that the altered microRNAs are associated with inflammation, innate immunity and cell cycle regulation. Taken together, the identified microRNAs and the pathways they modulate might represent candidates for novel molecular approaches for the treatment of patients with epilepsy.
Insights
MicroRNA expression changes in epilepsy models offer new treatment targets. Specific microRNAs (miR-142-5p, miR-331-3p, miR-30a-5p) were altered across acute and chronic epilepsy models.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Epilepsy impacts 50 million globally, with unknown causes in 65% of cases.
- MicroRNAs (non-coding RNAs) are implicated in epilepsy pathophysiology.
- Understanding microRNA dysregulation is crucial for novel epilepsy treatments.
Purpose of the Study:
- To compare microRNA expression patterns in the hippocampus across different epilepsy models.
- To identify specific microRNAs and pathways involved in epilepsy.
- To explore potential molecular targets for epilepsy treatment.
Main Methods:
- Utilized two chronic epilepsy models (pilocarpine, self-sustained status epilepticus) and an acute 6-Hz seizure model.
- Analyzed microRNA expression profiles in the hippocampus.
- Performed pathway analysis on differentially expressed microRNAs.
Main Results:
- Acute model showed predominantly upregulated microRNAs (146 within 6h).
- Chronic models exhibited balanced up/down-regulation of microRNAs.
- miR-142-5p, miR-331-3p, and miR-30a-5p were consistently deregulated across all models.
- Pathway analysis linked altered microRNAs to inflammation, innate immunity, and cell cycle regulation.
Conclusions:
- Identified key microRNAs (miR-142-5p, miR-331-3p, miR-30a-5p) common to acute and chronic epilepsy models.
- Demonstrated involvement of inflammation, immunity, and cell cycle pathways in epilepsy.
- These microRNAs and pathways represent potential targets for novel epilepsy therapies.
