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Open AccessArticle

Combined Treatment with Low-Dose Ionizing Radiation and Ketamine Induces Adverse Changes in CA1 Neuronal Structure in Male Murine Hippocampi

1
Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), 85764 Neuherberg, Germany
2
Chair of Radiation Biology, Technical University Munich (TUM), 80333 Munich, Germany
3
Department of Environmental Toxicology, University Uppsala, 75236 Uppsala, Sweden
4
Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), 80939 Munich, Germany
5
Research Unit Analytical Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH (HMGU), 85764 Neuherberg, Germany
6
Department of Immunology, Genetics and Pathology, Uppsala University, 75185 Uppsala, Sweden
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(23), 6103; https://doi.org/10.3390/ijms20236103
Received: 29 October 2019 / Revised: 29 November 2019 / Accepted: 2 December 2019 / Published: 3 December 2019
(This article belongs to the Section Molecular Toxicology)
In children, ketamine sedation is often used during radiological procedures. Combined exposure of ketamine and radiation at doses that alone did not affect learning and memory induced permanent cognitive impairment in mice. The aim of this study was to elucidate the mechanism behind this adverse outcome. Neonatal male NMRI mice were administered ketamine (7.5 mg kg−1) and irradiated (whole-body, 100 mGy or 200 mGy, 137Cs) one hour after ketamine exposure on postnatal day 10. The control mice were injected with saline and sham-irradiated. The hippocampi were analyzed using label-free proteomics, immunoblotting, and Golgi staining of CA1 neurons six months after treatment. Mice co-exposed to ketamine and low-dose radiation showed alterations in hippocampal proteins related to neuronal shaping and synaptic plasticity. The expression of brain-derived neurotrophic factor, activity-regulated cytoskeleton-associated protein, and postsynaptic density protein 95 were significantly altered only after the combined treatment (100 mGy or 200 mGy combined with ketamine, respectively). Increased numbers of basal dendrites and branching were observed only after the co-exposure, thereby constituting a possible reason for the displayed alterations in behavior. These data suggest that the risk of radiation-induced neurotoxic effects in the pediatric population may be underestimated if based only on the radiation dose. View Full-Text
Keywords: hippocampus; proteomics; BDNF; CA1 neurons; dendrite abnormality; Golgi staining; irradiation hippocampus; proteomics; BDNF; CA1 neurons; dendrite abnormality; Golgi staining; irradiation
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Hladik, D.; Buratovic, S.; Von Toerne, C.; Azimzadeh, O.; Subedi, P.; Philipp, J.; Winkler, S.; Feuchtinger, A.; Samson, E.; Hauck, S.M.; Stenerlöw, B.; Eriksson, P.; Atkinson, M.J.; Tapio, S. Combined Treatment with Low-Dose Ionizing Radiation and Ketamine Induces Adverse Changes in CA1 Neuronal Structure in Male Murine Hippocampi. Int. J. Mol. Sci. 2019, 20, 6103.

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