Exposure to 56 Fe irradiation accelerates normal brain aging and produces deficits in spatial learning and memory Barbara Shukitt-Hale a, * , Gemma Casadesus b , Amanda N. Carey a , Bernard M. Rabin c , James A. Joseph a a USDA-ARS, Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA b Institute of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA c Department of Psychology, UMBC, 1000 Hilltop Circle, Baltimore, MD 21250, USA Received 16 February 2005; received in revised form 27 October 2006; accepted 12 November 2006 Abstract Previous studies have shown that radiation exposure, particularly to particles of high energy and charge (HZE particles) such as 56 Fe, produces deficits in spatial learning and memory. These adverse behavioral effects are similar to those seen in aged animals. It is possible that these shared effects may be produced by the same mechanism. For example, an increased release of reactive oxygen species, and the subsequent oxidative stress and inflammatory damage caused to the central nervous system, is likely responsible for the deficits seen in aging and following irradiation. Therefore, dietary antioxidants, such as those found in fruits and vegetables, could be used as counter- measures to prevent the behavioral changes seen in these conditions. Both aged and irradiated rats display cognitive impairment in tests of spatial learning and memory such as the Morris water maze and the radial arm maze. These rats have decrements in the ability to build spatial representations of the environment, and they utilize non-spatial strategies to solve tasks. Furthermore, they show a lack of spatial preference, due to a decline in the ability to process or retain place (position of a goal with reference to a ‘‘map’’ provided by the con- figuration of numerous cues in the environment) information. These declines in spatial memory occur in measures dependent on both reference and working memory, and in the flexibility to reset mental images. These results show that irradiation with 56 Fe high-energy particles produces age-like decrements in cognitive behavior that may impair the ability of astronauts, particularly middle-aged ones, to perform critical tasks during long-term space travel beyond the magnetosphere. Published by Elsevier Ltd on behalf of COSPAR. Keywords: Cognitive; Oxidative stress; Inflammation; Antioxidants; Countermeasures; Morris water maze 1. Introduction Future missions in space, such as to Mars, may involve long-term travel beyond the magnetic field of the Earth, subjecting astronauts to radiation hazards posed by solar flares and galactic cosmic rays, consisting of protons, alpha particles, and particles of high energy and charge (HZE particles). Exposure of astronauts to these radiation sourc- es may affect their ability to successfully complete mission requirements. Previous studies have shown that exposure to radiation produces deficits in neurochemistry and behavior. Interestingly, these adverse behavioral effects are similar to those seen in aged animals. It therefore becomes important to undertake a more thorough evalua- tion of the behavioral effects of radiation in comparison to aging, the mechanisms by which both affect behavior, and possible nutritional modification procedures (e.g., antioxi- dants, phytochemicals) to offset the deleterious effects of both. Research from our laboratories and others has shown that exposure of rodents (primarily Sprague–Dawley rats 2–4 months of age) to HZE particles, primarily 600 MeV or 1 GeV 56 Fe, can produce profound deficits in behavior and neurochemistry, and these changes are similar to those seen in aged animals (Joseph et al., 1992, 1998, 2000), as 0273-1177/$30 Published by Elsevier Ltd on behalf of COSPAR. doi:10.1016/j.asr.2006.11.005 * Corresponding author. Tel.: +1 617 556 3118. E-mail address: barbara.hale@tufts.edu (B. Shukitt-Hale). www.elsevier.com/locate/asr Advances in Space Research 39 (2007) 1087–1092