title: Cosmic radiation exposure and persistent cognitive dysfunction.
abstract: The Mars mission will result in an inevitable exposure to cosmic radiation that has been shown to cause cognitive impairments in rodent models, and possibly in astronauts engaged in deep space travel. Of particular concern is the potential for cosmic radiation exposure to compromise critical decision making during normal operations or under emergency conditions in deep space. Rodents exposed to cosmic radiation exhibit persistent hippocampal and cortical based performance decrements using six independent behavioral tasks administered between separate cohorts 12 and 24 weeks after irradiation. Radiation-induced impairments in spatial, episodic and recognition memory were temporally coincident with deficits in executive function and reduced rates of fear extinction and elevated anxiety. Irradiation caused significant reductions in dendritic complexity, spine density and altered spine morphology along medial prefrontal cortical neurons known to mediate neurotransmission interrogated by our behavioral tasks. Cosmic radiation also disrupted synaptic integrity and increased neuroinflammation that persisted more than 6 months after exposure. Behavioral deficits for individual animals correlated significantly with reduced spine density and increased synaptic puncta, providing quantitative measures of risk for developing cognitive impairment. Our data provide additional evidence that deep space travel poses a real and unique threat to the integrity of neural circuits in the brain.
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Vipan K
authors.initials: VK
authors.lastname: Parihar
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Barrett D
authors.initials: BD
authors.lastname: Allen
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Chongshan
authors.initials: C
authors.lastname: Caressi
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Kwok
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Esther
authors.initials: E
authors.lastname: Chu
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Katherine K
authors.initials: KK
authors.lastname: Tran
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Nicole N
authors.initials: NN
authors.lastname: Chmielewski
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Erich
authors.initials: E
authors.lastname: Giedzinski
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Munjal M
authors.initials: MM
authors.lastname: Acharya
authors.affiliation: Department of Radiation Oncology, Eastern Virginia Medical School, Norfolk, VA 23507, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Britten
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Janet E
authors.initials: JE
authors.lastname: Baulch
authors.affiliation: Department of Radiation Oncology, University of California, Irvine, CA 92697-2695, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Limoli
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000528:radiation effects; D002452:Cell Count; D060825:Cognitive Dysfunction / Q000209:etiology*; D003359:Cosmic Radiation / Q000009:adverse effects*; D003712:Dendrites / Q000473:pathology / Q000528:radiation effects; D000076122:Disks Large Homolog 4 Protein / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D007249:Inflammation / Q000209:etiology; D008297:Male; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000528:radiation effects*; D017397:Prefrontal Cortex / Q000166:cytology / Q000528:radiation effects; D017208:Rats, Wistar
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse