title: Central nervous system effects of whole-body proton irradiation.
abstract: Space missions beyond the protection of Earth's magnetosphere expose astronauts to an environment that contains ionizing proton radiation. The hazards that proton radiation pose to normal tissues, such as the central nervous system (CNS), are not fully understood, although it has been shown that proton radiation affects the neurogenic environment, killing neural precursors and altering behavior. To determine the time and dose-response characteristics of the CNS to whole-body proton irradiation, C57BL/6J mice were exposed to 1 GeV/n proton radiation at doses of 0-200 cGy and behavioral, physiological and immunohistochemical end points were analyzed over a range of time points (48 h-12 months) postirradiation. These experiments revealed that proton radiation exposure leads to: 1. an acute decrease in cell division within the dentate gyrus of the hippocampus, with significant differences detected at doses as low as 10 cGy; 2. a persistent effect on proliferation in the subgranular zone, at 1 month postirradiation; 3. a decrease in neurogenesis at doses as low as 50 cGy, at 3 months postirradiation; and 4. a decrease in hippocampal ICAM-1 immunoreactivity at doses as low as 10 cGy, at 1 month postirradiation. The data presented contribute to our understanding of biological responses to whole-body proton radiation and may help reduce uncertainty in the assessment of health risks to astronauts. These findings may also be relevant to clinical proton beam therapy.
authors.affiliation: a  Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642.
authors.forename: Tara Beth
authors.initials: TB
authors.lastname: Sweet
authors.forename: Nirlipta
authors.initials: N
authors.lastname: Panda
authors.forename: Amy M
authors.initials: AM
authors.lastname: Hein
authors.forename: Shoshana L
authors.initials: SL
authors.lastname: Das
authors.forename: Sean D
authors.initials: SD
authors.lastname: Hurley
authors.forename: John A
authors.initials: JA
authors.lastname: Olschowka
authors.forename: Jacqueline P
authors.initials: JP
authors.lastname: Williams
authors.forename: M Kerry
authors.initials: MK
authors.lastname: O'Banion
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D001921:Brain / Q000166:cytology / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007249:Inflammation / Q000209:etiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000528:radiation effects; D011522:Protons / Q000009:adverse effects*; D013026:Space Flight; D014916:Whole-Body Irradiation / Q000009:adverse effects*
chemical_list: D011522:Protons