Neonatal Exposure to Low-Dose Ionizing Radiation in Mice Developmental Neurotoxic Effects of Single and Fractionated Doses and Interaction with Nicotine

Sammanfattning: 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.