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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 murine hippocampi.

Int. J. Mol. Sci. 20:2103 (2019)
Publ. Version/Full Text DOI PMC
Open Access Gold
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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, Cs-137) 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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Hippocampus ; Proteomics ; Bdnf ; Ca1 Neurons ; Dendrite Abnormality ; Golgi Staining ; Irradiation; Synaptic Plasticity; Neonatal Exposure; Dendritic Growth; Bdnf; Defects; Protein; Children; Dynamics; Sedation; Cortex
ISSN (print) / ISBN 1422-0067
e-ISSN 1661-6596
Journal International Journal of Molecular Sciences
Quellenangaben Volume: 20, Issue: 23, Pages: , Article Number: 2103 Supplement: ,
Publisher MDPI
Publishing Place Basel
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Radiation Biology (ISB)
CF Metabolomics & Proteomics (CF-MPC)
Research Unit Analytical Pathology (AAP)