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Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects.
Jimenez-Mateos, Eva M; Engel, Tobias; Merino-Serrais, Paula; McKiernan, Ross C; Tanaka, Katsuhiro; Mouri, Genshin; Sano, Takanori; O'Tuathaigh, Colm; Waddington, John L; Prenter, Suzanne; Delanty, Norman; Farrell, Michael A; O'Brien, Donncha F; Conroy, Ronán M; Stallings, Raymond L; DeFelipe, Javier; Henshall, David C.
Afiliação
  • Jimenez-Mateos EM; Department of Physiology and Medical Physics and Centre for Study of Neurological Disorders, Royal College of Surgeons in Ireland, Dublin, Ireland.
Nat Med ; 18(7): 1087-94, 2012 Jul.
Article em En | MEDLINE | ID: mdl-22683779
ABSTRACT
Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Convulsões / Fármacos Neuroprotetores / Inativação Gênica / MicroRNAs Limite: Adult / Animals / Humans / Male / Middle aged Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Irlanda

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Convulsões / Fármacos Neuroprotetores / Inativação Gênica / MicroRNAs Limite: Adult / Animals / Humans / Male / Middle aged Idioma: En Revista: Nat Med Assunto da revista: BIOLOGIA MOLECULAR / MEDICINA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Irlanda