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Space radiation‐induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK
Author(s) -
Manda Kailash,
Ueno Megumi,
Anzai Kazunori
Publication year - 2008
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2008.00611.x
Subject(s) - dentate gyrus , neurogenesis , doublecortin , oxidative stress , malondialdehyde , hippocampal formation , melatonin , hippocampus , population , chemistry , medicine , endocrinology , biology , neuroscience , environmental health
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.