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.

journal_name

Radiat Res

journal_title

Radiation research

authors

Lowe XR,Bhattacharya S,Marchetti F,Wyrobek AJ

doi

10.1667/RR1389.1

subject

Has Abstract

pub_date

2009-01-01 00:00:00

pages

53-65

issue

1

eissn

0033-7587

issn

1938-5404

pii

RR1389

journal_volume

171

pub_type

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