Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice.

Abstract

MicroRNAs perform important roles in the post-transcriptional regulation of gene expression. Sequencing as well as functional studies using antisense oligonucleotides indicate important roles for microRNAs during the development of epilepsy through targeting transcripts involved in neuronal structure, gliosis and inflammation. MicroRNA-22 (miR-22) has been reported to protect against the development of epileptogenic brain networks through suppression of neuroinflammatory signalling. Here, we used mice with a genetic deletion of miR-22 to extend these insights. Mice lacking miR-22 displayed normal behaviour and brain structure and developed similar status epilepticus after intraamygdala kainic acid compared to wildtype animals. Continuous EEG monitoring after status epilepticus revealed, however, an accelerated and exacerbated epilepsy phenotype whereby spontaneous seizures began sooner, occurred more frequently and were of longer duration in miR-22-deficient mice. RNA sequencing analysis of the hippocampus during the period of epileptogenesis revealed a specific suppression of inflammatory signalling in the hippocampus of miR-22-deficient mice. Taken together, these findings indicate a role for miR-22 in establishing early inflammatory responses to status epilepticus. Inflammatory signalling may serve anti-epileptogenic functions and cautions the timing of anti-inflammatory interventions for the treatment of status epilepticus.

• Authors: Luiz F Almeida Silva, Cristina R Reschke, Ngoc T Nguyen, Elena Langa, Amaya Sanz-Rodriguez, Rogerio R Gerbatin, Fernanda R Temp, Mayara L de Freitas, Ronan M Conroy, Gary P Brennan, Tobias Engel, David C Henshall
• Journal: Molecular brain (Mol Brain) Vol. 13 Issue 1 Pg. 114 (08 21 2020) ISSN: 1756-6606 [Electronic] England
• PMID: 32825833 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MicroRNAs
• Mirn22 microRNA, mouse

Topics

• Animals
• Disease Progression
• Down-Regulation (genetics)
• Epilepsy (genetics, pathology)
• Female
• Gene Deletion
• Inflammation (genetics, pathology)
• Male
• Mice
• MicroRNAs (genetics, metabolism)
• Phenotype
• Signal Transduction
• Status Epilepticus (genetics)
• Transcription, Genetic