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Combined Treatment with Low-Dose Ionizing Radiation and Ketamine Induces Adverse Changes in CA1 Neuronal Structure in Male Murine Hippocampi
German Res Ctr Environm Hlth GmbH HMGU, Helmholtz Zentrum Munchen, Inst Radiat Biol, D-85764 Neuherberg, Germany;Tech Univ Munich, Chair Radiat Biol, D-80333 Munich, Germany.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
German Res Ctr Environm Hlth GmbH HMGU, Helmholtz Zentrum Munchen, Res Unit Prot Sci, D-80939 Munich, Germany.ORCID iD: 0000-0002-4132-4322
German Res Ctr Environm Hlth GmbH HMGU, Helmholtz Zentrum Munchen, Inst Radiat Biol, D-85764 Neuherberg, Germany.
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2019 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 20, no 23, article id 6103Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
MDPI, 2019. Vol. 20, no 23, article id 6103
Keywords [en]
hippocampus, proteomics, BDNF, CA1 neurons, dendrite abnormality, Golgi staining, irradiation
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:uu:diva-402388DOI: 10.3390/ijms20236103ISI: 000504428300285PubMedID: 31817026OAI: oai:DiVA.org:uu-402388DiVA, id: diva2:1388489
Funder
Swedish Radiation Safety AuthorityAvailable from: 2020-01-24 Created: 2020-01-24 Last updated: 2020-01-24Bibliographically approved

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