MiRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132

Eva M. Jimenez-Mateos, Isabella Bray, Amaya Sanz-Rodriguez, Tobias Engel, Ross C. McKiernan, Genshin Mouri, Katsuhiro Tanaka, Takanori Sano, Julie Saugstad, Roger P. Simon, Raymond L. Stallings, David C. Henshall

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

When an otherwise harmful insult to the brain is preceded by a brief, noninjurious stimulus, the brain becomes tolerant, and the resulting damage is reduced. Epileptic tolerance develops when brief seizures precede an episode of prolonged seizures (status epilepticus). MicroRNAs (miRNAs) are small, noncoding RNAs that function as post-transcriptional regulators of gene expression. We investigated how prior seizure preconditioning affects the miRNA response to status epilepticus evoked by intra-amygdalar kainic acid in mice. The miRNA was extracted from the ipsilateral CA3 subfield 24 hours after focal-onset status epilepticus in animals that had previously received either seizure preconditioning (tolerance) or no preconditioning (injury), and mature miRNA levels were measured using TaqMan low-density arrays. Expression of 21 miRNAs was increased, relative to control, after status epilepticus alone, and expression of 12 miRNAs was decreased. Increased miR-132 levels were matched with increased binding to Argonaute-2, a constituent of the RNA-induced silencing complex. In tolerant animals, expression responses of >40% of the injury-group-detected miRNAs differed, being either unchanged relative to control or down-regulated, and this included miR-132. In vivo microinjection of locked nucleic acid-modified oligonucleotides (antagomirs) against miR-132 depleted hippocampal miR-132 levels and reduced seizure-induced neuronal death. Thus, our data strongly suggest that miRNAs are important regulators of seizure-induced neuronal death.

Original languageEnglish (US)
Pages (from-to)2519-2532
Number of pages14
JournalAmerican Journal of Pathology
Volume179
Issue number5
DOIs
StatePublished - Nov 2011
Externally publishedYes

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Status Epilepticus
MicroRNAs
Seizures
RNA-Induced Silencing Complex
Small Untranslated RNA
Neuroprotection
Kainic Acid
Wounds and Injuries
Brain
Microinjections
Regulator Genes
Oligonucleotides
Gene Expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Jimenez-Mateos, E. M., Bray, I., Sanz-Rodriguez, A., Engel, T., McKiernan, R. C., Mouri, G., ... Henshall, D. C. (2011). MiRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. American Journal of Pathology, 179(5), 2519-2532. https://doi.org/10.1016/j.ajpath.2011.07.036

MiRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. / Jimenez-Mateos, Eva M.; Bray, Isabella; Sanz-Rodriguez, Amaya; Engel, Tobias; McKiernan, Ross C.; Mouri, Genshin; Tanaka, Katsuhiro; Sano, Takanori; Saugstad, Julie; Simon, Roger P.; Stallings, Raymond L.; Henshall, David C.

In: American Journal of Pathology, Vol. 179, No. 5, 11.2011, p. 2519-2532.

Research output: Contribution to journalArticle

Jimenez-Mateos, EM, Bray, I, Sanz-Rodriguez, A, Engel, T, McKiernan, RC, Mouri, G, Tanaka, K, Sano, T, Saugstad, J, Simon, RP, Stallings, RL & Henshall, DC 2011, 'MiRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132', American Journal of Pathology, vol. 179, no. 5, pp. 2519-2532. https://doi.org/10.1016/j.ajpath.2011.07.036
Jimenez-Mateos, Eva M. ; Bray, Isabella ; Sanz-Rodriguez, Amaya ; Engel, Tobias ; McKiernan, Ross C. ; Mouri, Genshin ; Tanaka, Katsuhiro ; Sano, Takanori ; Saugstad, Julie ; Simon, Roger P. ; Stallings, Raymond L. ; Henshall, David C. / MiRNA expression profile after status epilepticus and hippocampal neuroprotection by targeting miR-132. In: American Journal of Pathology. 2011 ; Vol. 179, No. 5. pp. 2519-2532.
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