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Out-of-Field Hippocampus from Partial-Body Irradiated Mice Displays Changes in Multi-Omics Profile and Defects in Neurogenesis.
Pazzaglia, Simonetta; Tanno, Barbara; Antonelli, Francesca; Giardullo, Paola; Babini, Gabriele; Subedi, Prabal; Azimzadeh, Omid; Khan, Zohaib N; Oleksenko, Kateryna; Metzger, Fabian; Toerne, Christine von; Traynor, Damien; Medipally, Dinesh; Meade, Aidan D; Kadhim, Munira; Lyng, Fiona M; Tapio, Soile; Saran, Anna; Mancuso, Mariateresa.
Afiliación
  • Pazzaglia S; Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), 00123 Rome, Italy.
  • Tanno B; Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), 00123 Rome, Italy.
  • Antonelli F; Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), 00123 Rome, Italy.
  • Giardullo P; Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), 00123 Rome, Italy.
  • Babini G; Department of Physics, University of Pavia, 27100 Pavia, Italy.
  • Subedi P; Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), 00168 Rome, Italy.
  • Azimzadeh O; Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), Institute of Radiation Biology, D-85764 Neuherberg, Germany.
  • Khan ZN; Federal Office for Radiation Protection, Section Radiation Biology, D-85764 Oberschleissheim, Germany.
  • Oleksenko K; Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), Institute of Radiation Biology, D-85764 Neuherberg, Germany.
  • Metzger F; Federal Office for Radiation Protection, Section Radiation Biology, D-85764 Oberschleissheim, Germany.
  • Toerne CV; Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), Institute of Radiation Biology, D-85764 Neuherberg, Germany.
  • Traynor D; Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), Institute of Radiation Biology, D-85764 Neuherberg, Germany.
  • Medipally D; Research Unit Protein Science, HMGU, D-85764 Neuherberg, Germany.
  • Meade AD; Research Unit Protein Science, HMGU, D-85764 Neuherberg, Germany.
  • Kadhim M; Radiation and Environmental Science Centre, Technological University Dublin, D02 HW71 Dublin, Ireland.
  • Lyng FM; Radiation and Environmental Science Centre, Technological University Dublin, D02 HW71 Dublin, Ireland.
  • Tapio S; Radiation and Environmental Science Centre, Technological University Dublin, D02 HW71 Dublin, Ireland.
  • Saran A; Department of Biological and Medical Sciences, Oxford Brookes University (OBU), Oxford OX3 0BP, UK.
  • Mancuso M; Radiation and Environmental Science Centre, Technological University Dublin, D02 HW71 Dublin, Ireland.
Int J Mol Sci ; 22(8)2021 Apr 20.
Article en En | MEDLINE | ID: mdl-33924260
ABSTRACT
The brain undergoes ionizing radiation exposure in many clinical situations, particularly during radiotherapy for brain tumors. The critical role of the hippocampus in the pathogenesis of radiation-induced neurocognitive dysfunction is well recognized. The goal of this study is to test the potential contribution of non-targeted effects in the detrimental response of the hippocampus to irradiation and to elucidate the mechanisms involved. C57Bl/6 mice were whole body (WBI) or partial body (PBI) irradiated with 0.1 or 2.0 Gy of X-rays or sham irradiated. PBI consisted of the exposure of the lower third of the mouse body, whilst the upper two thirds were shielded. Hippocampi were collected 15 days or 6 months post-irradiation and a multi-omics approach was adopted to assess the molecular changes in non-coding RNAs, proteins and metabolic levels, as well as histological changes in the rate of hippocampal neurogenesis. Notably, at 2.0 Gy the pattern of early molecular and histopathological changes induced in the hippocampus at 15 days following PBI were similar in quality and quantity to the effects induced by WBI, thus providing a proof of principle of the existence of out-of-target radiation response in the hippocampus of conventional mice. We detected major alterations in DAG/IP3 and TGF-ß signaling pathways as well as in the expression of proteins involved in the regulation of long-term neuronal synaptic plasticity and synapse organization, coupled with defects in neural stem cells self-renewal in the hippocampal dentate gyrus. However, compared to the persistence of the WBI effects, most of the PBI effects were only transient and tended to decrease at 6 months post-irradiation, indicating important mechanistic difference. On the contrary, at low dose we identified a progressive accumulation of molecular defects that tended to manifest at later post-irradiation times. These data, indicating that both targeted and non-targeted radiation effects might contribute to the pathogenesis of hippocampal radiation-damage, have general implications for human health.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Irradiación Craneana / Proteoma / Metaboloma / Neurogénesis / Transcriptoma / Hipocampo Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Irradiación Craneana / Proteoma / Metaboloma / Neurogénesis / Transcriptoma / Hipocampo Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2021 Tipo del documento: Article País de afiliación: Italia