Related Experiment Video
Updated: May 28, 2026
Stereotactic Atlas-Guided Laser Capture Microdissection of Brain Regions Affected by Traumatic Injury
Published on: September 11, 2017
Neurotrophin-3 mRNA a putative target of miR21 following status epilepticus
Rashmi M Risbud1, Carolyn Lee, Brenda E Porter
1Division of Neurology, Department of Pediatrics at The Children's Hospital of Philadelphia, USA.
Abstract:
Status epilepticus induces a cascade of protein expression changes contributing to the subsequent development of epilepsy. By identifying the cascade of molecular changes that contribute to the development of epilepsy we hope to be able to design therapeutics for preventing epilepsy. MicroRNAs influence gene expression by altering mRNA stability and/or translation and have been implicated in the pathology of multiple diseases. MiR21 and its co-transcript miR21, microRNAs produced from either the 5' or 3' ends of the same precursor RNA strand, are increased in the hippocampus following status epilepticus. We have identified a miR21 binding site, in the 3' UTR of neurotrophin-3 that inhibits translation. Neurotrophin-3 mRNA levels decrease in the hippocampus following SE concurrent with the increase in miR21. MiR21 levels in cultured hippocampal neurons inversely correlate with neurotrophin-3 mRNA levels. Treatment of hippocampal neuronal cultures with excess K(+)Cl(-), a depolarizing agent mimicking the episode of status epilepticus, also results in an increase in miR21 and a decrease in neurotrophin-3 mRNA. MiR21 is a candidate for regulating neurotrophin-3 signaling in the hippocampus following status epilepticus.
Insights
MicroRNAs, such as miR21, increase after seizures and may regulate neurotrophin-3, potentially offering new epilepsy prevention strategies.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Epilepsy development involves molecular changes after status epilepticus (SE).
- MicroRNAs regulate gene expression and are implicated in disease pathology.
- miR21 levels rise in the hippocampus post-SE.
Purpose of the Study:
- To investigate the role of miR21 in neurotrophin-3 regulation following SE.
- To identify molecular targets of miR21 in the context of epilepsy development.
Main Methods:
- Analysis of microRNA and mRNA levels in hippocampal tissue and neuronal cultures.
- Identification of miR21 binding sites in target gene 3' UTRs.
- Experimental manipulation of neuronal activity using K(+)Cl(-) to mimic SE.
Main Results:
- A miR21 binding site was identified in the 3' UTR of neurotrophin-3, inhibiting translation.
- Neurotrophin-3 mRNA levels decreased in the hippocampus post-SE, correlating with increased miR21.
- Depolarizing conditions mimicking SE increased miR21 and decreased neurotrophin-3 in cultured neurons.
Conclusions:
- miR21 is a key regulator of neurotrophin-3 signaling in the hippocampus after status epilepticus.
- miR21-mediated regulation of neurotrophin-3 presents a potential therapeutic target for epilepsy prevention.
