Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK
Article first published online: 9 JUL 2008
© 2008 The Authors. Journal compilation © 2008 Blackwell Munksgaard
Journal of Pineal Research
Volume 45, Issue 4, pages 430–438, November 2008
How to Cite
Manda, K., Ueno, M. and Anzai, K. (2008), Space radiation-induced inhibition of neurogenesis in the hippocampal dentate gyrus and memory impairment in mice: ameliorative potential of the melatonin metabolite, AFMK. Journal of Pineal Research, 45: 430–438. doi: 10.1111/j.1600-079X.2008.00611.x
- Issue published online: 9 OCT 2008
- Article first published online: 9 JUL 2008
- Received April 26, 2008; accepted June 3, 2008.
- space radiation;
- memory impairment;
- oxidative stress;
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 N1-acetyl-N2-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 56Fe 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.