10779/rcsi.10791200.v1
Takanori Sano
Takanori
Sano
J P. Reynolds
J P.
Reynolds
Eva M. Jimenez-Mateos
Eva M.
Jimenez-Mateos
S Matsushima
S
Matsushima
W Taki
W
Taki
David C. Henshall
David C.
Henshall
MicroRNA-34a upregulation during seizure-induced neuronal death.
Royal College of Surgeons in Ireland
2019
Animals
Apoptosis
Argonaute Proteins
Benzothiazoles
Hippocampus
Immunoprecipitation
Kainic Acid
Male
Mice
Inbred C57BL
MicroRNAs
Protein Binding
Seizures
Toluene
Tumor Suppressor Protein p53
Up-Regulation
Physiology
Medical Physics
2019-11-22 16:58:02
Journal contribution
https://repository.rcsi.com/articles/journal_contribution/MicroRNA-34a_upregulation_during_seizure-induced_neuronal_death_/10791200
<p>MicroRNAs (miRNAs) are short, noncoding RNAs that function as posttranscriptional regulators of gene expression by controlling translation of mRNAs. A subset of miRNAs may be critical for the control of cell death, including the p53-regulated miRNA, miR-34a. Because seizures activate p53, and p53-deficient mice are reportedly resistant to damage caused by prolonged seizures, we investigated the role of miR-34a in seizure-induced neuronal death in vivo. Status epilepticus was induced by intra-amygdala microinjection of kainic acid in mice. This led to an early (2 h) multifold upregulation of miR-34a in the CA3 and CA1 hippocampal subfields and lower protein levels of mitogen-activated kinase kinase kinase 9, a validated miR-34a target. Immunoprecipitation of the RNA-induced silencing complex component, Argonaute-2, eluted significantly higher levels of miR-34a after seizures. Injection of mice with pifithrin-α, a putative p53 inhibitor, prevented miR-34a upregulation after seizures. Intracerebroventricular injection of antagomirs targeting miR-34a reduced hippocampal miR-34a levels and had a small modulatory effect on apoptosis-associated signaling, but did not prevent hippocampal neuronal death in models of either severe or moderate severity status epilepticus. Thus, prolonged seizures cause subfield-specific, temporally restricted upregulation of miR-34a, which may be p53 dependent, but miR-34a is probably not important for seizure-induced neuronal death in this model.</p>