Early-life X-ray exposure: at risk for premature aging and neurodegeneration?

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@phdthesis{990a2e108b8b4553a1bb8ba7af628312,
title = "Early-life X-ray exposure: at risk for premature aging and neurodegeneration?",
abstract = "Severe cognitive disorders can arise in brain tumour survivors due to cranial radiotherapy at a young age. Often this decline can be linked to hippocampal damage, which is especially important for memory and learning. In the past, it has been suggested that processes in radiation-induced cognitive deficits resemble ageing processes and represent an increased risk for the development of Alzheimer's disease (AD). In this thesis, both the short and long-term effects of radiation during a critical period of brain development were studied using a transgenic Alzheimer mouse model (3xTg), of which the phenotype resembles the human Alzheimer pathology. Ten days old mice were irradiated with 1.8 Gy and analyses for radiation-induced changes in the hippocampus were performed 1 and 24 hours after irradiation with X-rays, as well as at the age of 3 and 6 months. Despite an unchanged general health and global brain weight resulting from irradiation, we were able to identify specific defects in the hippocampus. More specifically, increased DNA damage could be observed 1 hour after irradiation. Furthermore, a persistent decrease in proliferating cells and changes in the number of stem cells in the hippocampal dentate gyrus at 3 and 6 months of age were observed. In addition, a radiation-induced increase in tau phosphorylation, an Alzheimer's characteristic, was observed at 6 months of age. In summary, our findings support the hypothesis that irradiation of the radiation-sensitive developing brain may negatively affectprocesses related to ageing and AD.",
keywords = "Thesis, Brain, X-ray exposure, aging",
author = "Manon Coone and Emma Coninx and Mieke Verslegers",
note = "Score=10",
year = "2018",
month = "6",
day = "29",
language = "English",
publisher = "KUL - Katholieke Universiteit Leuven",
school = "KUL - Katholieke Universiteit Leuven",

}

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TY - THES

T1 - Early-life X-ray exposure: at risk for premature aging and neurodegeneration?

AU - Coone, Manon

A2 - Coninx, Emma

A2 - Verslegers, Mieke

N1 - Score=10

PY - 2018/6/29

Y1 - 2018/6/29

N2 - Severe cognitive disorders can arise in brain tumour survivors due to cranial radiotherapy at a young age. Often this decline can be linked to hippocampal damage, which is especially important for memory and learning. In the past, it has been suggested that processes in radiation-induced cognitive deficits resemble ageing processes and represent an increased risk for the development of Alzheimer's disease (AD). In this thesis, both the short and long-term effects of radiation during a critical period of brain development were studied using a transgenic Alzheimer mouse model (3xTg), of which the phenotype resembles the human Alzheimer pathology. Ten days old mice were irradiated with 1.8 Gy and analyses for radiation-induced changes in the hippocampus were performed 1 and 24 hours after irradiation with X-rays, as well as at the age of 3 and 6 months. Despite an unchanged general health and global brain weight resulting from irradiation, we were able to identify specific defects in the hippocampus. More specifically, increased DNA damage could be observed 1 hour after irradiation. Furthermore, a persistent decrease in proliferating cells and changes in the number of stem cells in the hippocampal dentate gyrus at 3 and 6 months of age were observed. In addition, a radiation-induced increase in tau phosphorylation, an Alzheimer's characteristic, was observed at 6 months of age. In summary, our findings support the hypothesis that irradiation of the radiation-sensitive developing brain may negatively affectprocesses related to ageing and AD.

AB - Severe cognitive disorders can arise in brain tumour survivors due to cranial radiotherapy at a young age. Often this decline can be linked to hippocampal damage, which is especially important for memory and learning. In the past, it has been suggested that processes in radiation-induced cognitive deficits resemble ageing processes and represent an increased risk for the development of Alzheimer's disease (AD). In this thesis, both the short and long-term effects of radiation during a critical period of brain development were studied using a transgenic Alzheimer mouse model (3xTg), of which the phenotype resembles the human Alzheimer pathology. Ten days old mice were irradiated with 1.8 Gy and analyses for radiation-induced changes in the hippocampus were performed 1 and 24 hours after irradiation with X-rays, as well as at the age of 3 and 6 months. Despite an unchanged general health and global brain weight resulting from irradiation, we were able to identify specific defects in the hippocampus. More specifically, increased DNA damage could be observed 1 hour after irradiation. Furthermore, a persistent decrease in proliferating cells and changes in the number of stem cells in the hippocampal dentate gyrus at 3 and 6 months of age were observed. In addition, a radiation-induced increase in tau phosphorylation, an Alzheimer's characteristic, was observed at 6 months of age. In summary, our findings support the hypothesis that irradiation of the radiation-sensitive developing brain may negatively affectprocesses related to ageing and AD.

KW - Thesis

KW - Brain

KW - X-ray exposure

KW - aging

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/29786847

M3 - Master's thesis

PB - KUL - Katholieke Universiteit Leuven

ER -

ID: 4180623