Developmental disturbance of rat cerebral cortex following prenatal low-dose γ-irradiation: A quantitative study

Fukui, Yoshihiro; Hoshino, Kiyoshi; Hayasaka, Ichirô; Inouye, Minoru; Kameyama, Yoshiro

doi:10.1016/0014-4886(91)90129-z

Cited by 27 publications

(16 citation statements)

References 19 publications

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“…DTI and KB, CaBP, and SMI-32 staining were compared visually to identify anatomical structures, such as the cortical 6-layered structure (I–VI), corpus callosum, cingulum, external capsule, and anterior commissure, using the rat brain atlas [20]. We defined the 6 layers of the cerebral cortex based on cytoarchitecture, with reference to a previous paper [22] that shows the laminar structures of the primary somatosensory cortex of rats that had received different doses of X-irradiation on gestational day 15.…”

Section: Methodsmentioning

confidence: 99%

Diffusion Tensor Imaging of Brain Abnormalities Induced by Prenatal Exposure to Radiation in Rodents

et al. 2014

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We assessed brain abnormalities in rats exposed prenatally to radiation (X-rays) using magnetic resonance imaging (MRI) and histological experiments. Pregnant rats were divided into 4 groups: the control group (n = 3) and 3 groups that were exposed to different radiation doses (0.5, 1.0, or 1.5 Gy; n = 3 each). Brain abnormalities were assessed in 32 neonatal male rats (8 per group). Ex vivo T2-weighted imaging and diffusion tensor imaging (DTI) were performed using 11.7-T MRI. The expression of markers of myelin production (Kluver–Barrera staining, KB), nonpyramidal cells (calbindin-D28k staining, CaBP), and pyramidal cells (staining of the nonphosphorylated heavy-chain neurofilament SMI-32) were histologically evaluated. Decreased brain volume, increased ventricle volume, and thinner cortices were observed by MRI in irradiated rats. However, no abnormalities in the cortical 6-layered structure were observed via KB staining in radiation-exposed rats. The DTI color-coded map revealed a dose-dependent reduction in the anisotropic signal (vertical direction), which did not represent reduced numbers of pyramidal cells; rather, it indicated a signal reduction relative to the vertical direction because of low nerve cell density in the entire cortex. We conclude that DTI and histological experiments are useful tools for assessing cortical and hippocampal abnormalities after prenatal exposure to radiation in rats.

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Section: Methodsmentioning

confidence: 99%

Diffusion Tensor Imaging of Brain Abnormalities Induced by Prenatal Exposure to Radiation in Rodents

et al. 2014

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“…In mice and rats, at least, no malformations of the brain develop following exposure to doses lower than the level of 0.2 Gy. Discernible tissue abnormalities of the cerebral cortex are induced in rats by prenatal y-irradiation of 0.27 Gy or more on day 15 of gestation (Fukui et al, 1991). Significantly small brains at adulthood are produced following prenatal exposure to 0.5 Gy or more in rats and mice (Seo et al, 1982;Fukui et al, 1991;Sun et al, 1994).…”

Section: Threshold Radiation Dose In Inducing Malformationsmentioning

confidence: 99%

“…Discernible tissue abnormalities of the cerebral cortex are induced in rats by prenatal y-irradiation of 0.27 Gy or more on day 15 of gestation (Fukui et al, 1991). Significantly small brains at adulthood are produced following prenatal exposure to 0.5 Gy or more in rats and mice (Seo et al, 1982;Fukui et al, 1991;Sun et al, 1994). On the other hand, in the cerebellum tissue abnormality is produced in rats by at least 1 Gy irradiation at 6 days after birth (Inouye and Kameyama, 1986).…”

Section: Threshold Radiation Dose In Inducing Malformationsmentioning

confidence: 99%

“…One of the early changes in the cell observed 3 hours after exposure to X-rays is nuclear pyknosis (Takeuchi et al, 1976;Hayashi and Kameyama, 1979;Takeuchi and Murakami, 1979;Harmon and Allan, 1988), which is characteristic of apoptosis (Kerr et al, 1972;Wyllie et al, 1980;Tomei and Cope, 1991). The nuclear condensation is paralleled by a condensation of the cytoplasm with well-preserved external membranes sealing cellular contents within the cells (Fig.…”

Section: Radiation-induced Cell Death Is By Apoptosismentioning

confidence: 99%

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Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Inouye

1995

Congenital Anomalies

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The developing mammalian brain is highly susceptible to ionizing radiation.A significant increase in small head size and mental retardation has been noted in prenatally exposed survivors of the atomic bombing, with the highest risk in those exposed during 8-15 weeks after fertilization. This stage corresponds to day 13 of pregnancy for mice and day 15 for rats in terms of brain development. The initial damage produced by radiation at this stage is cell death in the ventricular zone (VZ) of the brain mantle, the radiosensitive germinal cell population. During histogenesis of the cerebellum, on the other hand, the external granular layer (EGL) is also radiosensitive. Although extensive cell death results in microcephaly and histological abnormality, both VZ and EGL have an ability to recover from a considerable cell loss and form the normal structure of the central nervous system. The number of cell deaths to induce tissue abnormalities in adult brain rises in the range of 15-25% of the germinal cell population; and the threshold doses are about 0.3 Gy for cerebral defects and 1 Gy for cerebellar anomalies in both mice and rats. A similar threshold level is suggested in human cases in induction of mental retardation.Radiation-induced cell death in the VZ and EGL has been revealed as apoptosis, by the nuclear and cytoplasmic condensation, transglutaminase activation, required macromolecular synthesis, and internucleosomal DNA cleavage. Apoptosis of the germinal cell is assumed to eliminate acquired genetic damage. Once an abnormality in DNA has been induced and fixed in a germinal cell, it would be greatly amplified during future proliferation, bringing with it the risk of producing malformations and tumors. These cells would commit suicide when injured for replacement by healthy cells, rather than undertake DNA repair which is rarely complete. In fact they show very slow repair of cellular damage.Thus the high sensitivity of undifferentiated neural cells to the lethal effect of radiation may constitute a biological defense mechanism.

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“…As somal size correlates with the extent and complexity of dendritic arborization, this reduction suggests that pyramidal cells undergo atrophic changes in schizophrenia that may impair intercellular communication [212]. Noteworthy, several studies on prenatal X-irradiation have pointed to an impaired development of pyramidal cell dendrites [132,216,217] or to an atrophy of pyramidal cell dendrites following normal development [164].…”

Section: Possible Impact Of Alterations Of the Morphology Of The Cerementioning

confidence: 99%

Prenatal Programming of Depression and Schizophrenia?

Dafotakis¹,

Vehoff²,

Korr³

et al. 2002

Neuroembryol Aging

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In recent years the concept has been explored that the pathologies of depression and schizophrenia originate during intrauterine life. Several animal models have been developed to investigate the etiopathogenesis of both depression and schizophrenia. However, most of these models have focussed only on single aspects of the corresponding pathology, whereas integrated models using a ‘neural systems’ approach are missing. Over recent last years, our laboratory has developed two novel animal models related to depression and schizophrenia based on such a neural systems approach, using prenatal stress (PS) and prenatal low-dose X-irradiation (PLDI) as damaging agents. This paper provides a comprehensive overview on the cellular and molecular mechanisms mediating the damaging influence of PS and PLDI on the developing brain, and discuss these novel animal models in the context of the relevant literature. Both models provide rationales for future prophylactic interventions in perinatal and adult life, developed on the basis of a better understanding of the underlying mechanisms.

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Developmental disturbance of rat cerebral cortex following prenatal low-dose γ-irradiation: A quantitative study

Cited by 27 publications

References 19 publications

Diffusion Tensor Imaging of Brain Abnormalities Induced by Prenatal Exposure to Radiation in Rodents

Diffusion Tensor Imaging of Brain Abnormalities Induced by Prenatal Exposure to Radiation in Rodents

Radiation‐Induced Apoptosis and Developmental Disturbance of the Brain*

Prenatal Programming of Depression and Schizophrenia?

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