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CREB Signaling Mediates Dose-Dependent Radiation Response in the Murine Hippocampus Two Years after Total Body Exposure.
Hladik, Daniela; Dalke, Claudia; von Toerne, Christine; Hauck, Stefanie M; Azimzadeh, Omid; Philipp, Jos; Ung, Marie-Claire; Schlattl, Helmut; Rößler, Ute; Graw, Jochen; Atkinson, Michael J; Tapio, Soile.
Afiliación
  • Hladik D; Institute of Radiation Biology, Helmholtz Zentrum München GmbH , German Research Center for Environmental Health GmbH (HMGU) , 85764 Neuherberg , Germany.
  • Dalke C; Technical University Munich (TUM) , 80333 Munich , Germany.
  • von Toerne C; Institute of Developmental Genetics , HMGU , 85764 Neuherberg , Germany.
  • Hauck SM; Research Unit Protein Science , HMGU , 80939 Munich , Germany.
  • Azimzadeh O; Research Unit Protein Science , HMGU , 80939 Munich , Germany.
  • Philipp J; Institute of Radiation Biology, Helmholtz Zentrum München GmbH , German Research Center for Environmental Health GmbH (HMGU) , 85764 Neuherberg , Germany.
  • Ung MC; Institute of Radiation Biology, Helmholtz Zentrum München GmbH , German Research Center for Environmental Health GmbH (HMGU) , 85764 Neuherberg , Germany.
  • Schlattl H; Institute of Developmental Genetics , HMGU , 85764 Neuherberg , Germany.
  • Rößler U; Research Unit Medical Radiation Physics and Diagnostics , HMGU , 85764 Neuherberg , Germany.
  • Graw J; Federal Office for Radiation Protection , Department SG Radiation Protection and Health , 85764 Oberschleißheim , Germany.
  • Atkinson MJ; Institute of Developmental Genetics , HMGU , 85764 Neuherberg , Germany.
  • Tapio S; Institute of Radiation Biology, Helmholtz Zentrum München GmbH , German Research Center for Environmental Health GmbH (HMGU) , 85764 Neuherberg , Germany.
J Proteome Res ; 19(1): 337-345, 2020 01 03.
Article en En | MEDLINE | ID: mdl-31657930
The impact of low-dose ionizing radiation (IR) on the human brain has recently attracted attention due to the increased use of IR for diagnostic purposes. The aim of this study was to investigate low-dose radiation response in the hippocampus. Female B6C3F1 mice were exposed to total body irradiation with 0 (control), 0.063, 0.125, or 0.5 Gy. Quantitative label-free proteomic analysis of the hippocampus was performed after 24 months. CREB signaling and CREB-associated pathways were affected at all doses. The lower doses (0.063 and 0.125 Gy) induced the CREB pathway, whereas the exposure to 0.5 Gy deactivated CREB. Similarly, the lowest dose (0.063 Gy) was anti-inflammatory, reducing the number of activated microglia. In contrast, induction of activated microglia and reactive astroglia was found at 0.5 Gy, suggesting increased inflammation and astrogliosis, respectively. The apoptotic markers BAX and cleaved CASP-3 and oxidative stress markers were increased only at the highest dose. Since the activated CREB pathway plays a central role in learning and memory, these data suggest neuroprotection at the lowest dose (0.063 Gy) but neurodegeneration at 0.5 Gy. The response to 0.5 Gy resembles alterations found in healthy aging and thus may represent radiation-induced accelerated aging of the brain.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína de Unión a Elemento de Respuesta al AMP Cíclico / Hipocampo Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteína de Unión a Elemento de Respuesta al AMP Cíclico / Hipocampo Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: J Proteome Res Asunto de la revista: BIOQUIMICA Año: 2020 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Estados Unidos