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Elevation in plasma tRNA fragments precede seizures in human epilepsy.
Hogg, Marion C; Raoof, Rana; El Naggar, Hany; Monsefi, Naser; Delanty, Norman; O'Brien, Donncha F; Bauer, Sebastian; Rosenow, Felix; Henshall, David C; Prehn, Jochen Hm.
Afiliación
  • Hogg MC; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • Raoof R; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • El Naggar H; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • Monsefi N; Department of Anatomy, College of Medicine, University of Mosul, Mosul, Iraq.
  • Delanty N; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • O'Brien DF; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • Bauer S; Department of Neurology, Beaumont Hospital, Dublin, Ireland.
  • Rosenow F; Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • Henshall DC; Department of Physiology and Medical Physics, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
  • Prehn JH; FutureNeuro Research Centre, Royal College of Surgeons in Ireland, St. Stephen's Green, Dublin, Ireland.
J Clin Invest ; 129(7): 2946-2951, 2019 04 30.
Article en En | MEDLINE | ID: mdl-31039137
ABSTRACT
Transfer RNAs (tRNAs) are a major class of noncoding RNA. Stress-induced cleavage of tRNA is highly conserved and results in tRNA fragments. Here we find specific tRNA fragments in plasma are associated with epilepsy. Small RNA sequencing of plasma samples collected during video-EEG monitoring of focal epilepsy patients identified significant differences in three tRNA fragments (5', 5'AlaTGC, and 5'GluCTC) from controls. Levels of these tRNA fragments were higher in pre-seizure than post-seizure samples, suggesting they may serve as biomarkers of seizure risk in epilepsy patients. In vitro studies confirmed that production and extracellular release of tRNA fragments was lower after epileptiform-like activity in hippocampal neurons. We designed PCR-based assays to quantify tRNA fragments in a cohort of pre- and post-seizure plasma samples from focal epilepsy patients and healthy controls (n = 32/group). Receiver operating characteristic analysis indicated that tRNA fragments potently distinguished pre- from post-seizure patients (area under the curve of 0.8-0.95). Elevated tRNA fragments levels were not detected in patients with psychogenic non-epileptic seizures, and did not result from medication tapering. This study identifies a novel class of epilepsy biomarker and reveals the potential existence of prodromal molecular patterns in blood that could be used to predict seizure risk.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN de Transferencia / Epilepsias Parciales / Ácidos Nucleicos Libres de Células Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: J Clin Invest Año: 2019 Tipo del documento: Article País de afiliación: Irlanda

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: ARN de Transferencia / Epilepsias Parciales / Ácidos Nucleicos Libres de Células Tipo de estudio: Clinical_trials / Prognostic_studies Límite: Adult / Female / Humans / Male Idioma: En Revista: J Clin Invest Año: 2019 Tipo del documento: Article País de afiliación: Irlanda