title: Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK.
abstract: Evaluation of potential health effects from high energy charged particle radiation exposure during long duration space travel is important for the future of manned missions. Cognitive health of an organism is considered to be maintained by the capacity of hippocampal precursors to proliferate and differentiate. Environmental stressors including irradiation have been shown to inhibit neurogenesis and are associated with the onset of cognitive impairments. The present study reports on the protective effects of N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK), a melatonin metabolite, against high energy charged particle radiation-induced oxidative damage to the brain. We observed that radiation exposure (2.0 Gy of 500 MeV/nucleon (56)Fe beams, a ground-based model of space radiation) impaired the spatial memory of mice at later intervals without affecting the motor activities. AFMK pretreatment significantly ameliorated these neurobehavioral ailments. Radiation-induced changes in the population of immature and proliferating neurons in the dentate gyrus were localized using anti-doublecortin (Dcx) and anti-Ki-67 expression. AFMK pretreatment significantly inhibited the loss of Dcx and Ki-67 positive cells. Moreover, AFMK pretreatment ameliorated the radiation-induced augmentation of protein carbonyls and 4-hydroxyalkenal + malondialdehyde (MDA + HAE) in the brain and maintained the total antioxidant capacity of plasma and nonprotein sulfhydryl contents in brain.
authors.affiliation: National Institute of Radiological Science, Chiba, Japan. kailashmanda@gmail.com
authors.forename: Kailash
authors.initials: K
authors.lastname: Manda
authors.forename: Megumi
authors.initials: M
authors.lastname: Ueno
authors.forename: Kazunori
authors.initials: K
authors.lastname: Anzai
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D049109:Cell Proliferation; D003359:Cosmic Radiation / Q000009:adverse effects*; D018891:Dentate Gyrus / Q000187:drug effects / Q000528:radiation effects*; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism; D007735:Kynuramine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008550:Melatonin; D008568:Memory / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000528:radiation effects; D055495:Neurogenesis / Q000187:drug effects / Q000528:radiation effects*; D009479:Neuropeptides / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009483:Neuropsychological Tests; D018384:Oxidative Stress / Q000528:radiation effects; D050050:Protein Carbonylation / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000975:Antioxidants; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D018696:Neuroprotective Agents; D007735:Kynuramine; C041550:N-acetyl-N-formyl-5-methoxykynurenamine; D008550:Melatonin