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Title: Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

Abstract

Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are alsomore » down regulated in normal human aging and Alzheimer's disease.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
Life Sciences Division
OSTI Identifier:
946736
Report Number(s):
LBNL-1438E
Journal ID: ISSN 0033-7587; RAREAE; TRN: US0901152
DOE Contract Number:  
DE-AC02-05CH11231
Resource Type:
Journal Article
Journal Name:
Radiation Research
Additional Journal Information:
Journal Name: Radiation Research; Journal ID: ISSN 0033-7587
Country of Publication:
United States
Language:
English
Subject:
59; AGING; BRAIN; CONTAMINATION; DISEASES; GENES; IONIZING RADIATIONS; IRRADIATION; MICE; PATIENTS; RADIATIONS; RADIOTHERAPY

Citation Formats

Lowe, Xiu R, Bhattacharya, Sanchita, Marchetti, Francesco, and Wyrobek, Andrew J. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease. United States: N. p., 2008. Web.
Lowe, Xiu R, Bhattacharya, Sanchita, Marchetti, Francesco, & Wyrobek, Andrew J. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease. United States.
Lowe, Xiu R, Bhattacharya, Sanchita, Marchetti, Francesco, and Wyrobek, Andrew J. Fri . "Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease". United States. https://www.osti.gov/servlets/purl/946736.
@article{osti_946736,
title = {Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease},
author = {Lowe, Xiu R and Bhattacharya, Sanchita and Marchetti, Francesco and Wyrobek, Andrew J.},
abstractNote = {Understanding the cognitive and behavioral consequences of brain exposures to low-dose ionizing radiation has broad relevance for health risks from medical radiation diagnostic procedures, radiotherapy, environmental nuclear contamination, as well as earth orbit and space missions. Analyses of transcriptome profiles of murine brain tissue after whole-body radiation showed that low-dose exposures (10 cGy) induced genes not affected by high dose (2 Gy), and low-dose genes were associated with unique pathways and functions. The low-dose response had two major components: pathways that are consistently seen across tissues, and pathways that were brain tissue specific. Low-dose genes clustered into a saturated network (p < 10{sup -53}) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified 9 neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose radiation, in the aging human brain (unirradiated), and in brain tissue from patients with Alzheimer's disease. Mice exposed to high-dose radiation did not show these effects and associations. Our findings indicate that the molecular response of the mouse brain within a few hours after low-dose irradiation involves the down-regulation of neural pathways associated with cognitive dysfunctions that are also down regulated in normal human aging and Alzheimer's disease.},
doi = {},
journal = {Radiation Research},
issn = {0033-7587},
number = ,
volume = ,
place = {United States},
year = {2008},
month = {6}
}