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Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling

BACKGROUND: The harmful consequences of in utero irradiation on learning and memory have been recognised but the molecular mechanisms behind the damage are still unknown. RESULTS: Using a mass spectrometry-based approach, we investigated the long-term changes in the global cortical and hippocampal p...

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Autores principales: Kempf, Stefan J., von Toerne, Christine, Hauck, Stefanie M., Atkinson, Michael J., Benotmane, Mohammed A., Tapio, Soile
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647474/
https://www.ncbi.nlm.nih.gov/pubmed/26578848
http://dx.doi.org/10.1186/s12953-015-0083-4
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author Kempf, Stefan J.
von Toerne, Christine
Hauck, Stefanie M.
Atkinson, Michael J.
Benotmane, Mohammed A.
Tapio, Soile
author_facet Kempf, Stefan J.
von Toerne, Christine
Hauck, Stefanie M.
Atkinson, Michael J.
Benotmane, Mohammed A.
Tapio, Soile
author_sort Kempf, Stefan J.
collection PubMed
description BACKGROUND: The harmful consequences of in utero irradiation on learning and memory have been recognised but the molecular mechanisms behind the damage are still unknown. RESULTS: Using a mass spectrometry-based approach, we investigated the long-term changes in the global cortical and hippocampal proteome 6 months after 0.1, 0.5 and 1.0 Gy in utero X-ray irradiation delivered on embryonic day 11 in male C57Bl/6 J offspring. We noted alterations in several signalling pathways involved in cognition, the transcription factor cAMP response element-binding protein (CREB) playing a central role. Immunoblotting of CREB and phosphorylated CREB (Ser133) showed an altered expression profile at all doses in the hippocampus and at 0.5 and 1.0 Gy in the cortex. The greatest reduction in the phospho-CREB level was seen at 1.0 Gy in the hippocampus. It was accompanied by enhanced expression of postsynaptic density protein 95 (PSD95), suggesting effect on synaptic plasticity in neuronal dendrites. CONCLUSIONS: As the CREB signalling pathway plays a crucial role in neuronal plasticity and long-term memory formation in the brain, the radiation-induced alterations of this pathway seen here are in good agreement with the cognitive dysfunction seen in in utero irradiated populations. These data contribute to a deeper biological understanding of molecular mechanisms behind the long-term damage induced by relatively low doses of ionising radiation during gestation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0083-4) contains supplementary material, which is available to authorized users.
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spelling pubmed-46474742015-11-18 Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling Kempf, Stefan J. von Toerne, Christine Hauck, Stefanie M. Atkinson, Michael J. Benotmane, Mohammed A. Tapio, Soile Proteome Sci Research BACKGROUND: The harmful consequences of in utero irradiation on learning and memory have been recognised but the molecular mechanisms behind the damage are still unknown. RESULTS: Using a mass spectrometry-based approach, we investigated the long-term changes in the global cortical and hippocampal proteome 6 months after 0.1, 0.5 and 1.0 Gy in utero X-ray irradiation delivered on embryonic day 11 in male C57Bl/6 J offspring. We noted alterations in several signalling pathways involved in cognition, the transcription factor cAMP response element-binding protein (CREB) playing a central role. Immunoblotting of CREB and phosphorylated CREB (Ser133) showed an altered expression profile at all doses in the hippocampus and at 0.5 and 1.0 Gy in the cortex. The greatest reduction in the phospho-CREB level was seen at 1.0 Gy in the hippocampus. It was accompanied by enhanced expression of postsynaptic density protein 95 (PSD95), suggesting effect on synaptic plasticity in neuronal dendrites. CONCLUSIONS: As the CREB signalling pathway plays a crucial role in neuronal plasticity and long-term memory formation in the brain, the radiation-induced alterations of this pathway seen here are in good agreement with the cognitive dysfunction seen in in utero irradiated populations. These data contribute to a deeper biological understanding of molecular mechanisms behind the long-term damage induced by relatively low doses of ionising radiation during gestation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12953-015-0083-4) contains supplementary material, which is available to authorized users. BioMed Central 2015-11-16 /pmc/articles/PMC4647474/ /pubmed/26578848 http://dx.doi.org/10.1186/s12953-015-0083-4 Text en © Kempf et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Kempf, Stefan J.
von Toerne, Christine
Hauck, Stefanie M.
Atkinson, Michael J.
Benotmane, Mohammed A.
Tapio, Soile
Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title_full Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title_fullStr Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title_full_unstemmed Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title_short Long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
title_sort long-term consequences of in utero irradiated mice indicate proteomic changes in synaptic plasticity related signalling
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4647474/
https://www.ncbi.nlm.nih.gov/pubmed/26578848
http://dx.doi.org/10.1186/s12953-015-0083-4
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