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Gene expression changes in mouse brain after exposure to low-dose ionizing radiation

Author: E. Yin, D.O. Nelson, M.A. Coleman et al.

Reference: Int. J. Radiat. Biol. ― 2003. ― Vol. 79, № 10. ― P. 759–775.

Keywords: gene expression, metabolic function, DNA

Abstract: PURPOSE: To characterize the cellular functions associated with the altered transcript profiles of mouse brain exposed to low-dose in vivo gamma-irradiation.

MATERIALS AND METHODS: Cerebral RNA was isolated at 30 min and 4 h after whole-body irradiation at 0.1 or 2 Gy, hybridized to random oligonucleotide arrays, and evaluated for time and dose-response patterns by multifactorial analyses.

RESULTS: Brain irradiation modulated the expression patterns of 1574 genes, of which 855 showed more than 1.5-fold variation. about 30% of genes showed dose-dependent variations, including genes exclusively affected by 0.1 Gy. About 60% of genes showed time-dependent variation with more genes affected at 30 min than at 4 h. Early changes involved signal transduction, ion regulation and synaptic signalling. Later changes involved metabolic functions including myelin and protein synthesis. Low-dose radiation also modulated the expression of genes involved in stress response, cell-cycle control and DNA synthesis/repair.

CONCLUSIONS: Doses of 0.1 Gy induced changes in gene expression that were qualitatively different from those at 2 Gy. The findings suggest that low-dose irradiation of the brain induces the expression of genes involved in protective and reparative functions, while down-modulating genes involved in neural signalling activity.

URL: http://www.ncbi.nlm.nih.gov/pubmed/20399419

Fetal irradiation interferes with adult cognition in the nonhuman primate.

Author: Friedman H.R., Selemon L.D.

Reference: Biol. Psychiatry. — 2010. — Vol. 68, № 1. — P. 108–111

Keywords: early gestation exposure, schizophrenia, fetally irradiated macaque monkeys

Abstract: BACKGROUND: Exposure to x-irradiation in early gestation has been shown to disrupt normal thalamocortical development in the monkey and thereby model one key feature of the neuropathology of schizophrenia. However, the effect of fetal irradiation on cognitive functions that are vulnerable in schizophrenia (e.g., working memory) has not been examined.

METHODS: Four fetally irradiated macaque monkeys (FIMs) and four age-matched controls (CONs) were tested as juveniles (12-30 months) and again as adults ( approximately 5 years) on delayed spatial response (DR), a working memory task that is dependent on intact prefrontal cortical circuitry.

RESULTS: As juveniles, seven of eight monkeys learned DR; one FIM refused to test. Performance in the two groups was not different. As adults, only one FIM achieved criterion on DR. Three of four FIMs did not reach criterion at the 0-sec delay interval of the DR task, whereas all four CONs mastered DR at the maximum tested delay of 10 sec. FIMs completed fewer DR test sessions compared with CONs. In contrast, all FIMs and three of four CONs learned an associative memory task, visual pattern discrimination.

CONCLUSIONS: Fetal exposure to irradiation resulted in an adult-onset cognitive impairment in the working memory domain that is relevant to understanding the developmental etiology of schizophrenia.

URL: http://www.ncbi.nlm.nih.gov/pubmed/20399419

EEG source analysis of chronic fatigue syndrome

Author: Flor-Henry P., Lind J.C., Koles Z.J.

Reference: Psychiatry Res. — 2010. — Vol. 181, № 2. — P. 155–164.

Keywords: chronic fatigue syndrome, EEG

Abstract: Sixty-one dextral, unmedicated women with chronic fatigue syndrome (CFS) diagnosed according to the Fukuda criteria (1994) and referred for investigation by rheumatologists and internists were studied with quantitative EEG (43 channels) at rest with eyes open and during verbal and spatial cognitive activation. The EEGs from the patients were compared with recordings from 80 dextral healthy female controls. Only those subjects who could provide 20 1-s artefact-free segments of EEG were admitted into the study. The analysis consisted of the identification of the spatial patterns in the EEGs that maximally differentiated the two groups and the estimation of the cortical source distributions underlying these patterns. Spatial patterns were analyzed in the alpha (8-13Hz) and beta (14-20Hz) bands and the source distributions were estimated using the Borgiotti-Kaplan BEAMFORMER algorithm. The results indicate that the spatial patterns identified were effective in separating the two groups, providing a minimum correct retrospective classification rate of 72% in both frequency bands while the subjects were at rest to a maximum of 83% in the alpha band during the verbal cognitive condition. Underlying cortical source distributions showed significant differences between the two groups in both frequency bands and in all cognitive conditions. Lateralized cortical differences were evident between the two groups in the both frequency bands during both the verbal and spatial cognitive conditions. During these active cognitive conditions, the CFS group showed significantly greater source-current activity than the controls in the left frontal-temporal-parietal regions of the cortex.

URL: http://www.ncbi.nlm.nih.gov/pubmed/20006474

Extreme sensitivity of adult neurogenesis to low doses of X-irradiation

Author: S. Mizumatsu, M.L. Monje, D.R. Morhardt et al.

Reference: Cancer Res. ― 2003. ― Vol. 63, № 14. ― P. 4021–4027.

Keywords: cognitive impairment, subgranular zone, hippocampal dentate gyrus, X-ray

Abstract: Therapeutic irradiation of the brain is associated with a number of adverse effects, including cognitive impairment. Although the pathogenesis of radiation-induced cognitive injury is unknown, it may involve loss of neural precursor cells from the subgranular zone (SGZ) of the hippocampal dentate gyrus and alterations in new cell production (neurogenesis). Young adult male C57BL mice received whole brain irradiation, and 6-48 h later, hippocampal tissue was assessed using immunohistochemistry for detection of apoptosis and numbers of proliferating cells and immature neurons. Apoptosis peaked 12 h after irradiation, and its extent was dose dependent. Forty-eight h after irradiation, proliferating SGZ cells were reduced by 93-96%; immature neurons were decreased from 40 to 60% in a dose-dependent fashion. To determine whether acute cell sensitivity translated into long-term changes, we quantified neurogenesis 2 months after irradiation with 0, 2, 5, or 10 Gy. Multiple injections of BrdUrd were given to label proliferating cells, and 3 weeks later, confocal microscopy was used to determine the percentage of BrdUrd-labeled cells that showed mature cell phenotypes. The production of new neurons was significantly reduced by X-rays; that change was dose dependent. In contrast, there were no apparent effects on the production of new astrocytes or oligodendrocytes. Measures of activated microglia indicated that changes in neurogenesis were associated with a significant inflammatory response. Given the known effects of radiation on cognitive function and the relationship between hippocampal neurogenesis and associated memory formation, our data suggest that precursor cell radiation response and altered neurogenesis may play a contributory if not causative role in radiation-induced cognitive impairment.

URL: http://www.ncbi.nlm.nih.gov/pubmed/12874001

European Commission. Radiation protection 100. Guidance for protection of unborn children and infants irradiated due to parental medical exposures.

Reference: Directorate-General Environment, Nuclear Safety, and Civil Protection, 1998. — 30 p.

Abstract: Whole article in English available on web.

URL: http://ec.europa.eu/energy/nuclear/radiation_protection/doc/publication/100_en.pdf

Epidemiology of non-cancer diseases among Chernobyl accident recovery operation workers

Author: V.A. Buzunov, N.P. Strapko, Ye.A. Pirogova et al.

Reference: International Journal of Radiation Medicine. — 2001. — Vol. 3, № 3–4. — P. 9–25.

Effects of prenatal brain irradiation as a result of the Chernobyl accident

Author: A.I. Nyagu, K.N. Loganovsky, R. Pott-Born et al.

Reference: International Journal of Radiation Medicine. — 2004. — Vol. 6, № 1–4. — P. 91–107.

Keywords: Chernobyl accident, brain damage in utero, dosimetry, psychometry, neuropsychiatric and psychological disorders.

Abstract: One of the grave consequences of the Chernobyl accident was the in utero irradiation of children. It was therefore important to study possible effects of prenatal irradiation resulted from the Chernobyl accident on neuromental health of the in utero irradiated children. A cohort of 154 children born between April 26th,1986 and February 26th,1987 to mothers who had been evacuated from Prypiat to Kiev,and 143 classmates from Kiev were examined. The Wechsler Intelligence Scale for Children (WISC),the Achenbach and Rutter A(2) tests were used for the children. School performance was also assessed. Mothers were examined with the verbal subscale of the Wechsler Adults Intelligence Scale (WAIS),the Zung Self-Rating Depression Scale (SDS),PTSD scales (Impact of Events Scale and Irritability,Depression,Anxiety Scales) and the General Health Questionnaire (GHQ-28). Neuropsychiatric diseases were diagnosed according to ICD-10. Individual dose reconstruction of the children exposed in utero was carried out considering internal and external exposure. The ICRP Publication-88 was applied for calculation of effective fetal, brain and thyroid internal doses for children of both groups. The mean effective fetal equivalent doses (M±SD) in the exposed group is 65.4±33.9 mSv and in the control group 1.2±0.3 mSv. Prenatal equivalent brain doses were 19.2±11.3 mSv and 0.8±0.2 mSv for the exposed and control groups,respectively. Thyroid doses in utero were 760.4±631.8.1 mSv and 44.5±43.3 mSv for the exposed and control groups,correspondingly. There were 20 children from Pripyat town (13.2%) who had been exposed in utero in total doses >100 mSv and there were 52 children from Pripyat town (33.8%) who had been exposed in utero to thyroid doses >1 Sv. The prenatally exposed children show significantly more diseases of the nervous system and mental disorders. Significant differences on intelligence and emotional and behavioral
disorders of exposed children in comparison to the control group were revealed….

URL: http://www.mns.gov.ua/files/rm/PDF/6_15.pdf

Effect of low doses of ionising radiation in infancy on cognitive function in adulthood: Swedish population based cohort study

Author: P. Hall, H.O. Adami, D. Trichopoulos et al.

Reference: BMJ. ― 2004. ― Vol. 328, № 7430. ― P. 19–24.

Keywords: cognitive function, Sweden, learning ability, spatial recognition, infancy

Abstract:

OBJECTIVE:To determine whether exposure to low doses of ionising radiation in infancy affects cognitive function in adulthood.

DESIGN: Population based cohort study.

SETTING: Sweden.

PARTICIPANTS: 3094 men who had received radiation for cutaneous haemangioma before age 18 months during 1930-59.

MAIN OUTCOME MEASURES: Radiation dose to frontal and posterior parts of the brain, and association between dose and intellectual capacity at age 18 or 19 years based on cognitive tests (learning ability, logical reasoning, spatial recognition) and high school attendance.

RESULTS: The proportion of boys who attended high school decreased with increasing doses of radiation to both the frontal and the posterior parts of the brain from about 32% among those not exposed to around 17% in those who received > 250 mGy. For the frontal dose, the multivariate odds ratio was 0.47 (95% confidence interval 0.26 to 0.85, P for trend 0.0003) and for the posterior dose it was 0.59 (0.23 to 1.47, 0.0005). A negative dose-response relation was also evident for the three cognitive tests for learning ability and logical reasoning but not for the test of spatial recognition.

CONCLUSIONS: Low doses of ionising radiation to the brain in infancy influence cognitive abilities in adulthood.

URL:http://www.ncbi.nlm.nih.gov/pubmed/14703539

Effect of low dose ionizing radiation exposure in utero on cognitive function in adolescence

Author: K.S. Heiervang, S. Mednick, K. Sundet, B.R. Rund

Reference: Scand. J. Psychol. — 2010. — Vol. 51, № 3. — 210–215.

Keywords: Norway, IQ, prenatal exposure

Abstract: Radiation from the Chernobyl nuclear power plant meltdown greatly affected several Norwegian counties. The cognitive consequences of in utero exposure to radiation from the Chernobyl accident have been intensely debated. This study examines the cognitive outcomes for those Norwegians who were exposed as fetuses to the fallout from Chernobyl. The participants, 84 adolescents who were exposed in utero to radiation from the most contaminated areas in Norway and 94 adolescents from areas not contaminated by the radiation, were tested on verbal and nonverbal IQ. Two data analyses were conducted. First, using a control-group design, the IQ scores of exposed and unexposed adolescents were compared. Second, in a timing-of-exposure design, those exposed during the most sensitive period were contrasted with those exposed later in gestation. Adolescents exposed to low-dose ionizing radiation in utero scored significantly lower in full-scale IQ than unexposed adolescents. The difference was restricted to verbal IQ and was not evident for nonverbal IQ. The effect was not observed in exposed adolescents who had passed the most sensitive gestational period prior to the accident and thus were exposed to the radiation from Chernobyl exclusively after gestational week 16. These participants performed as well as the controls. Although the results should be interpreted cautiously due to the study’s nonrandomized design, the data add new and important support to the hypothesis that the Chernobyl accident may have had a subtle effect on the cognitive functioning of those exposed to low-dose ionizing radiation in utero during the most sensitive gestational period.

URL: http://www.ncbi.nlm.nih.gov/pubmed/20338021

Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer’s disease

Author: X.R. Lowe, S. Bhattacharya, F. Marchetti, A.J. Wyrobek

Reference: Radiat. Res. ― 2009. ― Vol. 171, № 1. ― P. 53–65.

Abstract: full text available on web.

URL: http://www.osti.gov/bridge/servlets/purl/946736-kPQEGv/946736.pdf

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