Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult mice
Autor: | Gaëtan Philippot, Sonja Buratovic, Synnöve Sundell-Bergman, Anders Fredriksson, Per Eriksson, Bo Stenerlöw |
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Rok vydání: | 2018 |
Předmět: |
Male
Paraquat medicine.medical_specialty Transcription Genetic medicine.drug_class 010501 environmental sciences Biology Motor Activity Toxicology 01 natural sciences Nicotine 03 medical and health sciences chemistry.chemical_compound Mice Neurochemical Dopamine Internal medicine medicine Animals Maze Learning 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Behavior Animal Dopaminergic Neurotoxicity Brain Dose-Response Relationship Radiation medicine.disease Mice Inbred C57BL Endocrinology medicine.anatomical_structure chemistry Animals Newborn Cerebral cortex Gamma Rays Sedative Anesthesia Female Neurotoxicity Syndromes medicine.drug |
Zdroj: | Journal of applied toxicology : JAT. 39(4) |
ISSN: | 1099-1263 |
Popis: | This thesis examines the developmental neurotoxic effects of exposure to low-dose ionizing radiation (IR), alone or together with xenobiotics, during a critical period of neonatal brain development in mice.During mammalian brain development there is a period called the brain growth spurt (BGS), which involves extensive growth and maturation of the brain. It is known that neonatal exposure during the BGS to xenobiotics can have a negative impact on neonatal brain development, resulting in impaired cognitive function in the adult mouse. In humans, the BGS starts during the third trimester of pregnancy and continues for approximately 2 years in the child. The present thesis has identified a defined critical period, during the BGS, when IR can induce developmental neurotoxicity in mice. The observed neurotoxicity was not dependent on sex or strain and manifested as altered neurobehaviour in the adult mouse. Furthermore, fractionated dose exposures appear to be as potent as a higher acute dose. The cholinergic system can be a target system for developmental neurotoxicity of IR, since alterations in adult mouse cholinergic system susceptibility were observed. Co-exposure to IR and nicotine exacerbated the behavioural disturbances and cholinergic system dysfunction. Furthermore, co-exposure with the environmental agent paraquat has indicated that the dopaminergic system can be a potential target. In this thesis, clinically relevant doses of IR and a sedative/anesthetic agent (ketamine) were shown to interact and exacerbate defects in adult mouse neurobehaviour, learning and memory, following neonatal exposure, at doses where the single agents did not have any impact on the measured variables. This indicates a shift in the dose-response curve for IR, towards lower doses, if exposure occurs during the neonatal brain development. In addition, co-exposed mice, showing cognitive defects, expressed elevated levels of tau protein in the cerebral cortex. Furthermore, exacerbation of neurochemical deviations were observed following co-exposure compared to irradiation alone.Further investigations of neurotoxic effects following fractionated or acute low-dose IR, modelling the clinical situation during repeated CT scans or levels of radiation deposited in non-target tissue during radiotherapy, and possible interaction effects with xenobiotics, is of great importance in the field of radioprotection. |
Databáze: | OpenAIRE |
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