EUROPEAN RADIATION RESEARCH 2012

Low-dose Irradiation Induced Mitochondrial Alterations in the Brain of Young Mice

18 Oct 2012, 16:38

1m

Poster Hall (Vietri sul Mare)

poster preferred Non-Cancer Effects Poster Session 3

Speaker

Katalin Lumniczky (National Research Institute for Radiobiology and Radiohygiene, Budapest, Hungary)

Description

Background: Central nervous system toxicity after high doses of irradiation is well documented. The biological effects of low doses are far less known. Accumulating data show, that low-dose irradiation might increase the incidence of ischemic cardiovascular diseases and the mechanisms by which this occurs is under intense investigation. However, much less attention is paid to low-dose radiation effects on the microvasculature of the brain and its microenvironment, although functional and/or morphological damage in these structures might be in great part responsible for the late non-ischemical neurological alterations after radiation. In our work we proposed to study low-dose irradiation induced mitochondrial damage in the whole brain and in the endothelial cells of the brain microvasculature. Methods: Since developing brain might be more susceptible to low-dose induced long-term alterations, we investigated 10-day old C57BL/6 mice. Animals were irradiated on their head with single doses of 0.1 or 2 Gy X-rays. 1, 3, 7 days and 1 month after irradiation mice were sacrificed, and single cell suspensions of the various brain regions made. Half of the brains were processed for biochemical measurements of enzyme activities of the respiratory chain in the mitochondrial membrane. The other halves were stained with Rhodamine 123 to evaluate alterations in the mitochondrial membrane potential and with Mitosox Red to determine the level of superoxide anions in the mitochondrial membrane. By costaining the cells with the endothelial specific marker CD31, we studied mitochondrial damage within the endothelial cells as well. Results: A reduction of cytochrome C oxidase activity was detected after irradiation with 2 Gy, while 0.1 Gy had only moderate effect compared to control. The other enzymes in the respiratory chain are under investigation. A moderate, dose-dependent increase was seen in the level of mitochondrial superoxide as well as in the level of mitochondrial membrane potential damage 3 days after irradiation, which normalized after 1 week. Mitochondrial damage in the CD31+ endothelial cells seems to be consistently higher than that found in the unfractionated brain cell suspension. Conclusions: Low-dose local irradiation induces moderate but detectable mitochondrial alterations both in the brain and in the endothelial cells of the microvascular compartment of the brain. This work was supported by the FP7 – CEREBRAD project.