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Neonatal Exposure to Low-Dose Ionizing Radiation in Mice: Developmental Neurotoxic Effects of Single and Fractionated Doses and Interaction with Nicotine
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
2015 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims to investigate the developmental neurotoxic effects of low-dose exposure to ionizing radiation, alone or together with nicotine, during a defined critical period of neonatal brain development in mice. 

Investigation of neurotoxic effects following fractionated or acute low-dose radiation, resembling the clinical situation during repeated CT scans or radiation delivered to non-target tissue during radiotherapy, and possible interaction effects with other agents, is of great importance for risk and safety evaluation.

During mammalian brain development there are defined critical periods for induction of developmental neurotoxic effects. One of these critical periods is called the brain growth spurt (BGS) and involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to low doses of radiation, as well as nicotine, can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. 

The present studies have shown that developmental neurotoxicity following low-dose irradiation can be induced during the same critical period of brain development as previously has been shown for chemicals. The observed neurotoxicity was manifested as altered spontaneous behaviour and habituation capacity, independent of sex, as well as elevated levels of an Alzheimer-related neuroprotein in the adult mouse. Furthermore, fractionated dose regimes seem to be as potent for induction of neurotoxicity and behavioural disturbances as an equivalent single acute dose. The cholinergic system can be a target system for developmental neurotoxicity of ionizing radiation, either alone or in combination with the cholinergic agent nicotine. Co-exposure to ionizing radiation and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction observed in these studies.

Further studies on developmental neurotoxic effects of low-dose neonatal irradiation and interaction with medical drugs and environmental pollutants are important for the field of radioprotection. 

Place, publisher, year, edition, pages
Uppsala, 2015. , 38 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:uu:diva-242816OAI: oai:DiVA.org:uu-242816DiVA: diva2:785255
Presentation
2015-03-16, Hörstadius, Norbyvägen 18a, Uppsala, 10:15 (English)
Opponent
Supervisors
Funder
EU, FP7, Seventh Framework Programme, 29552Swedish Radiation Safety Authority
Available from: 2015-03-19 Created: 2015-02-02 Last updated: 2015-03-19Bibliographically approved
List of papers
1. Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
Open this publication in new window or tab >>Neonatal exposure to a moderate dose of ionizing radiation causes behavioural defects and altered levels of tau protein in mice
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2014 (English)In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 45, 48-55 p.Article in journal (Refereed) Published
Abstract [en]

Medical use of ionizing radiation (IR) has great benefits for treatment and diagnostic imaging, butprocedures as computerized tomography (CT) may deliver a significant radiation dose to the patient.Recently, awareness has been raised about possible non-cancer consequences from low dose exposure toIR during critical phases of perinatal and/or neonatal brain development.In the present study neonatal NMRI mice were whole body irradiated with a single dose of gammaradiation (0; 350 and 500 mGy) on postnatal day 10 (PND 10). At 2 and 4 months of age, mice of bothsexes were observed for spontaneous behaviour in a novel home environment. The neuroproteinsCaMKII, GAP-43, synaptophysin and total tau in male mouse cerebral cortex and hippocampus wereanalysed 24 h post-irradiation and in adults at 6 months of age exposed to 0 or 500 mGy on PND 10.A significantly dose-response related deranged spontaneous behaviour in 2- and 4-month-old micewas observed, where both males and females displayed a modified habituation, indicating reducedcognitive function. The dose of 350 mGy seems to be a tentative threshold. Six-month-old male miceshowed a significantly increased level of total tau in cerebral cortex after irradiation to 500 mGy compared to controls. This demonstrates that a single moderate dose of IR, given during a defined criticalperiod of brain development, is sufficient to cause persistently reduced cognitive function. Moreover, anelevation of tau protein was observed in male mice displaying reduced cognitive function.

National Category
Other Natural Sciences
Identifiers
urn:nbn:se:uu:diva-240576 (URN)10.1016/j.neuro.2014.09.002 (DOI)000346955100006 ()25265567 (PubMedID)
Available from: 2015-01-08 Created: 2015-01-08 Last updated: 2017-06-30Bibliographically approved
2. Effects of fractionated low dose exposure to gamma radiation and the interaction with nicotine on behaviour in mice
Open this publication in new window or tab >>Effects of fractionated low dose exposure to gamma radiation and the interaction with nicotine on behaviour in mice
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(English)Manuscript (preprint) (Other academic)
National Category
Natural Sciences
Identifiers
urn:nbn:se:uu:diva-242814 (URN)
Available from: 2015-02-02 Created: 2015-02-02 Last updated: 2015-03-19

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