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 and environmental nuclear contamination as well as for Earth-orbit and space missions. Analyses of transcriptome profiles of mouse brain tissue after whole-body irradiation showed that low-dose exposures (10 cGy) induced genes not affected by high-dose radiation (2 Gy) and that 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 specific for brain tissue. Low-dose genes clustered into a saturated network (P < 10(-53)) containing mostly down-regulated genes involving ion channels, long-term potentiation and depression, vascular damage, etc. We identified nine neural signaling pathways that showed a high degree of concordance in their transcriptional response in mouse brain tissue after low-dose irradiation, 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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Xiu R
authors.initials: XR
authors.lastname: Lowe
authors.forename: Sanchita
authors.initials: S
authors.lastname: Bhattacharya
authors.forename: Francesco
authors.initials: F
authors.lastname: Marchetti
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wyrobek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000528:radiation effects*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects*; D003071:Cognition / Q000528:radiation effects*; D019295:Computational Biology; D016208:Databases, Factual; D004781:Environmental Exposure / Q000009:adverse effects*; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000528:radiation effects; D006801:Humans; D051379:Mice; D008875:Middle Aged; D009434:Neural Pathways / Q000528:radiation effects; D011829:Radiation Dosage; D015398:Signal Transduction / Q000528:radiation effects; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects; D014916:Whole-Body Irradiation / Q000009:adverse effects