On exploratory class missions to other planets astronauts will be
exposed to types and doses of radiation that are not experienced in low earth
orbit. While it is likely that the crew will consist of both male and female
astronauts, there has been little research on the effects of exposure to space
radiation on central nervous system function and cognitive performance
in female subjects. Because estrogen can function as a neuroprotectant, the
present experiments were designed to evaluate whether or not the presence
or absence of estrogen at the time of irradiation would affect the susceptibility
to the neurocognitive effects of exposure to 56Fe particles in
female rats. Capsules containing 17β-estradiol
or vehicle were implanted in ovariectomized rats three days prior to exposure 56Fe
particles (50-200 cGy, 1000 MeV/n). Cognitive performance was evaluated using
novel object recognition memory to measure learning and memory and operant
responding on an ascending fixed-ratio schedule to measure changes in
motivation and in the responsiveness to environmental contingencies. The
results indicated the estrogen does not function as a neuroprotectant to minimize
the cognitive effects of exposure to 56Fe particles. However, the
presence/absence of estrogen at the time of irradiation could modulate the
responsiveness of the subject to the disruptive effects of exposure to HZE
particles on the performance of specific cognitive tasks.
Cite this paper
B. Rabin, K. Carrihill-Knoll, L. Long, S. Pitts and B. Hale, "Effects of 17β-Estradiol on Cognitive Performance of Ovariectomized Female Rats Exposed to Space Radiation," Journal of Behavioral and Brain Science, Vol. 3 No. 1, 2013, pp. 67-73. doi: 10.4236/jbbs.2013.31007.
 F. A. Cucinotta, W. Schimmerling, P. B. Saganti, J. W. Wilson, L. E. Peterson, G. D. Badhwar and J. F. Dicello, “Space Radiation Cancer Risks and Uncertainties for Mars Missions,” Radiation Research, Vol. 156, No. 5, 2001, pp. 682-688.
 A. A. Edwards, “RBE of Radiations in Space and the Implications for Space Travel,” Physica Medica, Vol. 27, 2001, pp. 147-152.
 W. Schimmerling, F. A. Cucinotta and J. W. Wilson, “Radiation Risk and Human Space Exploration” Advances in Space Research, Vol. 31, No. 1, 2003, pp. 2734. doi:10.1016/S0273-1177(02)00653-1
 G. Casadesus, B. Shukitt-Hale, H. M. Stellwagen, M. A. Smith, B. M. Rabin and J. A. Joseph, “Hippocampal Neurogenesis and PSA-NCAM Expression Following Exposure to 56Fe Particles Mimics That Seen during Aging in Rats,” Experimental Gerontology, Vol. 40, No. 3, 2005, pp. 249-254. doi:10.1016/j.exger.2004.09.007
 N. Denisova, B. Shukitt-Hale, B, M. Rabin and J. A. Joseph, “Brain Signaling and Behavioral Responses Induced by Exposure to 56Fe Radiation,” Radiation Research, Vol. 158, No. 6, 2002, pp. 725-734.
 J. A. Joseph, B. Shukitt-Hale, J. McEwen and B. M. Rabin, “CNS-Induced Deficits of Heavy Particle Irradiation in Space: The Aging Connection,” Advances in Space Research, Vol. 25, No. 10, 2000, pp. 2057-2064.
 B. Shukitt-Hale, G. Casadesus, A. Carey, B. M. Rabin and J. A. Joseph, “Exposure to 56Fe Irradiation Accelerates Normal Brain Aging and Produces Deficits in Learning and Memory,” Advances in Space Research, Vol. 39, No. 6, 2007, pp. 1087-1092.
 L. Villasana, J. Rosenberg and J. Raber, “Sex-Dependent Effects of 56Fe Irradiation on Contextual Fear Conditioning in C57BL/6J Mice,” Hippocampus, Vol, 20, 2010, pp. 19-23.
 R. Vlkolinsky, T. Krucker, A. L. Smith, T. C. Lamp, G. A. Nelson and A. Obenhaus, “Effects of Lipopolysaccharide on 56Fe-Particle Radiation-Induced Impairment of Synaptic Plasticity in the Mouse Hippocampus,” Radiation Research, Vol. 168, No. 4, 2007, pp. 462-470.
 D. M. Davis, T. K. Jacobsen, S. Aliakbari and S. J. Y. Mizumori, “Differential Effects of Estrogen on Hippocampaland Stiratal-Dependent Learning,” Neurobiology of Learning and Memory, Vol. 84, No. 2, 2005, pp. 132137. doi:10.1016/j.nlm.2005.06.004
 L. A. M. Galea, “Gonadal Hormone Modulation of Neurogenesis in the Dentate Gyrus of Adult Male and Female Rodents,” Brain Research Reviews, Vol. 57, No. 2, 2008, pp. 332-341. doi:10.1016/j.brainresrev.2007.05.008
 J. Prange-Kiel and G. M. Rune, “Direct and Indirect Effects of Estrogen on Rat Hippocampus,” Neuroscience, Vol. 138, No. 3, 2006, pp. 756-772.
 M. G. Quinal, D. Hussain and E. G. Brake, “Use of Cognitive Strategies in Rats: The Role of Estradiol and Its Interaction with Dopamine,” Hormones and Behavior, Vol. 53, No. 1, 2008, pp. 185-191.
 F. Van Haaren, A. van Hest and R. P. W. Heinsbroek, “Behavioral Differences between Male and Female Rats: Effects of Gonadal Hormones in Learning and Memory,” Neuroscience and Biobehavioral Reviews, Vol. 14, No. 1, 1990, pp. 23-33. doi:10.1016/S0149-7634(05)80157-5
 M. Wallace, V. Luine, A. Arekkanos and M. Frankfurt, “Ovariectomized Rats Show Decreased Recognition Memory and Spine Density in the Hippocampus and Prefrontal Cortex,” Brain Research, Vol. 1176, No. 1, 2006, pp. 176-182. doi:10.1016/j.brainres.2006.07.064
 D. E. Brann, K. Dhandapani, C. Wakade, V. B. Mahesh and M. M. Khan, “Neurotrophic and Neuroprotective Actions of Estrogen: Basic Mechanisms and Clinical Implications,” Steroids, Vol. 72, No. 5, 2007, pp. 381-405.
 L. M. Garcia-Segura, I. Azcoitiaa and L. L. DonCarlos, “Neuroprotection by Estradiol,” Progress in Neurobiology, Vol. 63, No. 3, 2001, pp. 29-60.
 G. E. Gilles and S. McArthur, “Independent Influences of Sex Steroids of Systemic and Central Origin in a Rat Model of Parkinson’s Disease: A Contribution to SexSpecific Neuroprotection by Estrogens,” Hormones and Behavior, Vol. 57, No. 1, 2010, pp. 23-34.
 P. S. Green and J. W. Simpkins, “Neuroprotective Effects of Estrogens: Potential Mechanisms of Action,” International Journal of Developmental Neuroscience, Vol. 18, No. 4-5, 2000, pp. 347-358.
 L. Charalampopoulos, E. Remboutsika, A. N. Margoris and A. Gravanis, “Neurosteroids as Modulators of Neurogenesis and Neuronal Survival,” Trends in Endocrinology and Metabolism, Vol. 19, No. 8, 2008, pp. 300-307.
 D. E. Dluzen, “Estrogen Decreases Corpus Striatal Neurotoxicity in Response to 6-Hydroxydopamine,” Brain Research, Vol. 767, No. 2, 1997, pp. 340-344.
 D. E. Dluzen, “Neuroprotective Effects of Estrogen upon the Nigrostratal Dopaminergic System,” Journal of Neurocytology, Vol. 29, No. 5-6, 2000, pp. 387-399.
 J. Nilson, “Estradiol and Neurodegenerative Oxidative Stress,” Frontiers in Neuroendocrinology, Vol. 29, No. 4, 2008, pp. 463-475. doi:10.1016/j.yfrne.2007.12.005
 M. Kipp, S. Karakaya, J. Pawlak, G. Araujo-Wright, S. Arnold and C. Beyer, “Estrogen and the Development and Protection of Nigrostriatal Dopaminergic Neurons: Concerted Action of a Multitude of Signals, Protective Molecules, and Growth Factors,” Frontiers in Neuroendocrinology, Vol. 27, No. 4, 2006, pp. 376-390.
 E. Vegeto, V. Benedusi and A. Maggi, “Estrogen Anti-Inflammatory Activity in Brain: A Therapeutic Opportunity for Menopause and Neurodegenerative Diseases,” Frontiers in Neuroendocrinology, Vol. 29, No. 4, 2008, pp. 507-519. doi:10.1016/j.yfrne.2008.04.001
 J. W. Simpkins and J. A. Dykens, “Mitochondrial Mechanisms of Estrogen Neuroprotection,” Brain Research Reviews, Vol. 57, No. 2, 2008, pp. 421-430.
 J. D. Yager and J. Q. Chen, “Mitochondrial Estrogen Receptors—New Insights into Specific Functions,” Trends in Endocrinology & Metabolism, Vol. 18, No. 3, 2007, pp. 89-91. doi:10.1016/j.tem.2007.02.006
 M. Cordey, U. Gundimeda, R. Gopalakrishna and C. J. Pike, “Estrogen Activates Protein Kinase C in Neurons: Role in Neuroprotection,” Journal of Neurochemistry, Vol. 84, No. 6, 2003, pp. 1340-1348.
 K. M. Dhandapani and D. W. Brann, “Role of Astrocytes in Estrogen-mediated Neuroprotection,” Experimental Gerontology, Vol. 42, No. 1-2, 2007, pp. 70-75.
 C. L. Limoli, E. Giedsinski, H. Baure, R. Rola and J. R. Fike, “Redox Changes Induced Hippocampal Precursor Cells by Heavy Ion Irradiation,” Radiation and Environmental Biophysics, Vol. 46, No. 2, 2007, pp. 167-172.
 R. Rola, V. Sarkissian, A. Obenhaus, G. A. Nelson, S. Otsuka, C. L. Limoli and J. R. Fike, “High-LET Radiation Induces Inflammation and Persistent Changes in Markers of Hippocampal Neurogenesis,” Radiation Research, Vol. 164, No. 4, 2005, pp. 556-560.
 A. N. Carey, B. Shukitt-Hale, B. M Rabin and J. A. Joseph, “Interaction between Age and Exposure to 56Fe Particles on Behavior and Neurochemistry,” Advances in Space Research, Vol. 39, No. 6, 2007, pp. 987-993.
 J. A. Joseph, W. A. Hunt, B. M. Rabin and T. K. Dalton, “Possible ‘Accelerated Aging’ Induced by 56Fe Heavy Particle Irradiation: Implications for Manned Space Flights,” Radiation Research, Vol. 130, No. 1, 1991, pp. 88-93.
 J. A. Joseph, W. A. Hunt, B. M. Rabin, T. K. Dalton and A. H. Harris, “Deficits in Striatal Muscarinic Receptor Sensitivity Induced by 56Fe Heavy Particle Irradiation: Further ‘Age-Radiation’ Parallels,” Radiation Research, Vol. 135, No. 2, 1993, pp. 257-261. doi:10.2307/3578303
 J. O. Strom, E. Theodorsson and A. Theodorsson, “Order of Magnitude Differences Between Methods for Maintaining Physiological 17B-Oestradiol Concentration in Ovariectomized Rats,” Scandinavian Journal of Clinical and Laboratory Investigation, Vol. 68, No. 8, 2008, pp. 814-822. doi:10.1080/00365510802409703
 B. M. Rabin, K. L. Carrihill-Knoll, M. Hinchman, B. Shukitt-Hale, J. A. Joseph and B. C. Foster, “Effects of Heavy Particle Irradiation and Diet on Object Recognition Memory in Rats,” Advances in Space Research, Vol. 43, No. 8, 2009, pp. 1193-1199.
 B. M. Rabin, J. A. Joseph and B. Shukitt-Hale, “A Longitudinal Study of Operant Responding in Rats Irradiated When 2 Months Old,” Radiation Research, Vol. 164, No. 4, 2005, pp. 552-555. doi:10.1667/RR3349.1
 M. D. Lindner, M. A. Plone, J. M. Francis, T. J. Blane, J. D. Salmone and D. F. Emerich, “Rats with Partial Striatal Dopamine Depletions Exhibit Robust and Long-lasting Behavioral Deficits in a Simple Fixed-ratio Bar Pressing Task,” Behavioural Brain Research, Vol. 86, No. 1, 1997, pp. 25-40. doi:10.1016/S0166-4328(96)02240-1
 J. D. Salamone, “The Involvement of Nucleus Accumbens Dopamine in Appetitive and Aversive Motivation,” Behavioural Brain Research, Vol. 61, No. 2, 1994, 117133. doi:10.1016/0166-4328(94)90153-8
 J. D. Salamone and M. Correa, “Motivational Reviews of Reinforcement: Implications for Understanding the Behavioral Functions of Nucleus Accumbens Dopamine,” Behavioural Brain Research, Vol. 137, No. 1-2, 2002, pp. 3-25. doi:10.1016/S0166-4328(02)00282-6
 G. Keppel, “Design and Analysis: A Researcher’s Handbook,” 4th Edition, Prentice Hall, Upper Saddle River, 1991.
 M. M. McCarthy, “How It’s Made: Organisational Effects of Hormones on the Developing Brain,” Journal of Neuroendocrinology, Vol. 22, No. 7, 2010, pp. 736-742.
 T. Aubele, R. Kaufman, F. Montalmant and M. F. Kritzer, “Effects of Gonadectomy and Hormone Replacement on a Spontaneous Novel Object Recognition Task in Adult Male Rats,” Hormones and Behavior, Vol. 54, No. 2, 2008, pp. 244-252. doi:10.1016/j.yhbeh.2008.04.001
 R. B. Gibbs, “Testosterone and Estradiol Produce Different Effects on Cognitive Performance in Male Rats,” Hormones and Behavior, Vol. 48, No. 3, 2005, pp. 266277. doi:10.1016/j.yhbeh.2005.03.005
 J. S. Sutcliffe, K. M. Marshall and J. C. Neill, “Influence of Gender on Working and Spatial Memory in the Novel Object Recognition Task in the Rat,” Behavioural Brain Research, Vol. 177, No. 1, 2007, pp. 117-125.
 J. B. Becker, “Gender Differences in Dopaminergic Function in Striatum and Nucleus Accumbens,” Pharmacology Biochemistry and Behavior, Vol. 64, No. 4, 1999, pp. 803-812. doi:10.1016/S0091-3057(99)00168-9
 D. Mitsushima, K. Takase, T. Funabashi and F. Kimura, “Gonadal Steroids Maintain 24 h Acetylcholine Release in the Hippocampus: Organizational and Activational Effects in Behaving Rats,” Journal of Neuroscience, Vol. 29, No. 12, 2009, pp. 3808-3815.