Genetic deletion of microRNA-22 blunts the....pdf (3.79 MB)

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

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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.

Funding

CNPq foundation

Science Foundation Ireland awards 13/IA/1891 , 17/CDA/4708, 17/TIDA/5002, 16/RC/3948

European Regional Development Fund

FutureNeuro industry partners

CAPES/PDSE visiting scientist fellowships

Marie S Curie Individual Fellowship (EpimiRGen)

European Union Seventh Framework Programme (FP7/2007–2013) grant agreement n° 602130 (EpimiRNA)

History

Comments

The original article is available at https://molecularbrain.biomedcentral.com

Published Citation

Almeida Silva LF, et al. Genetic deletion of microRNA-22 blunts the inflammatory transcriptional response to status epilepticus and exacerbates epilepsy in mice. Mol Brain. 2020;13(1):114.

Publication Date

21 August 2020

PubMed ID

32825833

Department/Unit

  • FutureNeuro Centre
  • Physiology and Medical Physics
  • Public Health and Epidemiology

Research Area

  • Population Health and Health Services
  • Neurological and Psychiatric Disorders
  • Health Professions Education
  • Cancer

Publisher

BioMed Central

Version

  • Published Version (Version of Record)