Selective brain responses to acute and chronic low-dose X-ray irradiation in males and females.
Radiation exposure is known to have profound effects on the brain, leading to precursor cell dysfunction and debilitating cognitive declines [Nat. Med. 8 (2002) 955]. Although a plethora of data exist on the effects of high radiation doses, the effects of low-dose irradiation, such as ones received during repetitive diagnostic and therapeutic exposures, are still under-investigated [Am. J. Otolaryngol. 23 (2002) 215; Proc. Natl. Acad. Sci. USA 97 (2000) 889; Curr. Opin. Neurol. 16 (2003) 129]. Furthermore, most studies of the biological effects of ionizing radiation have been performed using a single acute dose, while clinically and environmentally relevant exposures occur predominantly under chronic/repetitive conditions. Here, we have used a mouse model to compare the effects of chronic/repetitive and acute low-dose radiation (LDR) exposure (0.5Gy) to ionizing radiation on the brain in vivo. We examined the LDR effects on p42/44 MAPK (ERK1/ERK2), CaMKII, and AKT signaling-the interconnected pathways that have been previously shown to be crucial for neuronal survival upon irradiation. We report perturbations in ERK1/2, AKT, and CREB upon acute and chronic/repetitive low-dose exposure in the hippocampus and frontal cortex of mice. These studies were paralleled by the analysis of radiation effects on neurogenesis and cellular proliferation. Repetitive exposure had a much more pronounced effect on cellular signaling and neurogenesis than acute exposure. These results suggest that studies of single acute exposures might be limited in terms of their predictive value. We also present the first evidence of sex differences in radiation-induced signaling in the hippocampus and frontal cortex. We show the role of estrogens in brain radiation responses and discuss the implications of the observed changes.
Silasi
Greg
G
Department of Psychology and Neuroscience, University of Lethbridge, Lethbridge, Alta., Canada T1K 3M4.
Diaz-Heijtz
Rochellys
R
Besplug
Jill
J
Rodriguez-Juarez
Rocio
R
Titov
Viktor
V
Kolb
Bryan
B
Kovalchuk
Olga
O
D000818:Animals; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009097:Multienzyme Complexes / Q000378:metabolism / Q000528:radiation effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects*; D010865:Pilot Projects; D011829:Radiation Dosage; D012737:Sex Factors; D015398:Signal Transduction / Q000528:radiation effects; D014965:X-Rays
D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins