Developping brain radiosensitivity

Role of exposure to low dose Radiation to induce Delayed Adult behavioral Defects "RadDef"

The brain is the final result of a series of well timed consecutive or concomitant waves of cellular proliferation, migration, and differentiation. Acute irradiation during pregnancy could selectively disturb these events to result in various forms of abnormalities such as microcephaly, reduced cortical thickness and mental retardation. Such events were previously described in epidemiological studies of the atomic bomb survivors of Hiroshima/Nagasaki.

Mice irradiated respectively with 0.2 Gy at day E11 and 1 Gy at day E12, tested by Morris Water Maze, showed later when adult (12 weeks), behavioral defects i.e. clear memory and learning defects. Moreover we showed that radiation induced a reduction in the neurite length in primary neurons isolated from the hippocampus, and an increased cell death of maturing neurons. Such events might interfere with a correct patterning of the brain and possibly lead later to cognitive deficits.

The mechanisms of radiation-induced central nervous system (CNS) disorders are still unclear, but several studies suggested the involvement of local inflammatory response upon oxidative stress. The identification of the molecular and proinflammatory signaling pathways, as well as the epigenetic (methylation) factors, should help to unravel the radiation delayed effects at low doses and link the observed behavioral phenotype with molecular and cellular data. The molecular aspects of the inflammatory response induced upon radiation exposure are investigated in the brain embryos few hours following low dose irradiation.

People: Benotmane Rafi