Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis

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Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis. / Verreet, Tine; Rangarajan, Janaki Raman; Quintens, Roel; Verslegers, Mieke; Lo, Adrian C.; Govaerts, Kristof; Neefs, Mieke; Leysen, Liselotte; Baatout, Sarah; Maes, Frederik; Himmelreich, Uwe; D'Hooge, Rudi; Moons, Lieve; Benotmane, Rafi.

In: Frontiers in Behavioral Neuroscience, Vol. 10, No. 83, 83, 04.05.2016, p. 1-18.

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Verreet, Tine ; Rangarajan, Janaki Raman ; Quintens, Roel ; Verslegers, Mieke ; Lo, Adrian C. ; Govaerts, Kristof ; Neefs, Mieke ; Leysen, Liselotte ; Baatout, Sarah ; Maes, Frederik ; Himmelreich, Uwe ; D'Hooge, Rudi ; Moons, Lieve ; Benotmane, Rafi. / Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis. In: Frontiers in Behavioral Neuroscience. 2016 ; Vol. 10, No. 83. pp. 1-18.

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@article{373cf8c7caca4108ae6afe9aaafe6c56,
title = "Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis",
abstract = "Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests.",
keywords = "brain development, cognition, microcephaly, MRI, radiation, sociability",
author = "Tine Verreet and Rangarajan, {Janaki Raman} and Roel Quintens and Mieke Verslegers and Lo, {Adrian C.} and Kristof Govaerts and Mieke Neefs and Liselotte Leysen and Sarah Baatout and Frederik Maes and Uwe Himmelreich and Rudi D'Hooge and Lieve Moons and Rafi Benotmane",
note = "Score=10",
year = "2016",
month = "5",
day = "4",
doi = "10.3389/fnbeh.2016.00083",
language = "English",
volume = "10",
pages = "1--18",
journal = "Frontiers in Behavioral Neuroscience",
issn = "1662-5153",
publisher = "Frontiers Media SA",
number = "83",

}

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TY - JOUR

T1 - Persistent Impact of In utero Irradiation on Mouse Brain Structure and Function Characterized by MR Imaging and Behavioral Analysis

AU - Verreet, Tine

AU - Rangarajan, Janaki Raman

AU - Quintens, Roel

AU - Verslegers, Mieke

AU - Lo, Adrian C.

AU - Govaerts, Kristof

AU - Neefs, Mieke

AU - Leysen, Liselotte

AU - Baatout, Sarah

AU - Maes, Frederik

AU - Himmelreich, Uwe

AU - D'Hooge, Rudi

AU - Moons, Lieve

AU - Benotmane, Rafi

N1 - Score=10

PY - 2016/5/4

Y1 - 2016/5/4

N2 - Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests.

AB - Prenatal irradiation is known to perturb brain development. Epidemiological studies revealed that radiation exposure during weeks 8-15 of pregnancy was associated with an increased occurrence of mental disability and microcephaly. Such neurological deficits were reproduced in animal models, in which rodent behavioral testing is an often used tool to evaluate radiation-induced defective brain functionality. However, up to now, animal studies suggested a threshold dose of around 0.30 Gray (Gy) below which no behavioral alterations can be observed, while human studies hinted at late defects after exposure to doses as low as 0.10 Gy. Here, we acutely irradiated pregnant mice at embryonic day 11 with doses ranging from 0.10 to 1.00 Gy. A thorough investigation of the dose-response relationship of altered brain function and architecture following in utero irradiation was achieved using a behavioral test battery and volumetric 3D T2-weighted magnetic resonance imaging (MRI). We found dose-dependent changes in cage activity, social behavior, anxiety-related exploration, and spatio-cognitive performance. Although behavioral alterations in low-dose exposed animals were mild, we did unveil that both emotionality and higher cognitive abilities were affected in mice exposed to ≥0.10 Gy. Microcephaly was apparent from 0.33 Gy onwards and accompanied by deviations in regional brain volumes as compared to controls. Of note, total brain volume and the relative volume of the ventricles, frontal and posterior cerebral cortex, cerebellum, and striatum were most strongly correlated to altered behavioral parameters. Taken together, we present conclusive evidence for persistent low-dose effects after prenatal irradiation in mice and provide a better understanding of the correlation between their brain size and performance in behavioral tests.

KW - brain development

KW - cognition

KW - microcephaly

KW - MRI

KW - radiation

KW - sociability

UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/20017554

UR - http://journal.frontiersin.org/article/10.3389/fnbeh.2016.00083/full

U2 - 10.3389/fnbeh.2016.00083

DO - 10.3389/fnbeh.2016.00083

M3 - Article

VL - 10

SP - 1

EP - 18

JO - Frontiers in Behavioral Neuroscience

JF - Frontiers in Behavioral Neuroscience

SN - 1662-5153

IS - 83

M1 - 83

ER -

ID: 1527351