Medical Radiology and Radiation Safety. 2017. Vol. 62. No. 2. P. 5-12

DOI: 10.12737/article_58f0b9572d7131.31568909

Neuromediator Exchange Dynamics in Rats at Late Periods After Exposure to 60Co g-Rays

K.V. Belokopytova1,2, O.V. Belov1, V.N. Gaevsky1, V.B. Narkevich3, V.S. Kudrin3, E.A. Krasavin1, A.S. Bazyan4

1. Institute for Nuclear Research, Dubna, Russia, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. ; 2. Institute of Genetics, Physiology and Plant Protection of the Moldovan Academy of Sciences, Chisinau, Moldova; 3. FSBI Zakusov Institute of Pharmacology, Moscow, Russia; 4. Institute of Higher Nervous Activity and Neurophysiology of RAS, Moscow, Russia

K.V. Belokopytova - Junior Researcher; O.V. Belov - PhD in Biology, Head of Sector; V.N. Gaevsky - Leading Engineer; V.B. Narkevich - PhD in Medicine, Researcher; V.S. Kudrin - PhD in medicine, Head of Laboratory; E.A. Krasavin - Corr. Member RAS, Acad., D. Sc. Biol., Director of Laboratory; A.S. Bazyan - Prof., D. Sc. Biol., Head of Laboratory


Purpose: Estimation of the 60Co γ-ray effect on the neuromediator exchange dynamics in the brain of rats of different age groups.

Material and methods: 20 male Sprague-Dawley rats with the weight of 190-210 g were used in the experiment. At the age of two months, animals were exposed to a single whole-body irradiation with 60Co γ-rays at the dose of 1 Gy. In 30 and 90 days after exposure, rats we killed by decapitation. The animals were tested at three and five months of age, respectively. The neuromediator exchange dynamics was estimated by measuring the concentrations of monoamines (dopamine, noradrenaline, and serotonin) and their metabolites in four brain regions including prefrontal cortex, hypothalamus, hippocampus, and striatum. The levels of substances were assessed using the high-performance liquid chromatography with electrochemical detection. The results of measurements were statistically analyzed with the one-way analysis of variance (ANOVA).

Results: Although the direct measurements seeking for changes at the same time points revealed a little effect of γ-rays on the monoamine metabolism, age-related dynamics of the neuromediator exchange was affected in many aspects. The most pronounced in alterations in the two-month monoamine exchange dynamics were observed in the prefrontal cortex, hypothalamus and hippocampus. It indicates the sensitivity of these brain structures to the action of γ-rays at doses about 1 Gy. In the prefrontal cortex, hippocampus and hypothalamus, radiation exposure affected dopamine and serotonin regulations in the manner that may indicate suppression of catecholamine degrading pathways dependent on monoamine oxidases A and B against the activation of metabolic processes associated with catechol-O-methyltransferase. The prefrontal cortex and hypothalamus additionally exhibited an accelerated decrease in levels of some neuromediators, as compared to the dynamics normally observed beyond the age of three months. At the same time, our study identified a resistance of striatal metabolic pathways to irradiation with γ-rays at the stated dose. A comparison of the obtained data with results of our previous experiments investigating the action of accelerated carbon ions confirmed our expectations that the effect of γ-rays on the dynamics of the neuromediator exchange is less pronounced than from heavy nuclei.

Conclusion: Made a hypothesis that, in the case of heavy ion exposure, more pronounced alterations in brain mediator systems lead to more intensive compensatory and regenerative processes in them. Consequently, it may change the normal dynamics of neuromediator exchange in the investigated post-irradiation periods and serve a reason not only for decrease but also for an abnormal increase in levels of monoamines and their metabolites after exposure. In general, results of the performed study contribute to understanding the neurotoxic effect of γ-rays in comparison with other radiation modalities that can potentially be useful for predicting late outcomes of cranial radiation therapy.

Key words: central nervous system, ionizing radiations, late effects, monoamines, metabolites


  1. Grigor'ev Yu.G., Ushakov I.B., Krasavin E.A. et al. Kosmicheskaya radiobiologiya za 55 let (k 50-letiyu GNC RF-IMBP RAN). Moscow: Ekonomika. 2013. 303 p. (In Russ.).
  2. Yin E., Nelson D.O., Coleman M.A. et al. Gene expression changes in mouse brain after exposure to low-dose ionizing radiation. Int. J. Radiat. Biol. 2003. Vol. 79. P. 759-775.
  3. Sanchez M.C., Benitez A., Ortloff L., Green L.M. Alterations in glutamate uptake in NT2-derived neurons and astrocytes after exposure to gamma radiation. Radiat. Res. 2009. Vol. 171. P. 41-52.
  4. Britten R.A., Davis L.K., Johnson A.M., et al. Low (20 cGy) doses of 1 GeV/u (56)Fe-particle radiation lead to a persistent reduction in the spatial learning ability of rats. Radiat. Res. 2012. Vol. 177. P. 146-151.
  5. Monje M.L., Mizumatsu S., Fike J.R., Palmer T.D. Irradiation induces neural precursor-cell dysfunction. Nat. Med. 2002. Vol. 8. P. 955-962.
  6. Mizumatsu S., Monje M.L., Morhardt D.R. et al. Extreme sensitivity of adult neurogenesis to low doses of x-irradiation. Cancer Res. 2003. Vol. 63. P. 4021-4027.
  7. Acharya M.M., Christie L.A., Lan M.L. et al. Human neural stem cell transplantation ameliorates radiation-induced cognitive dysfunction. Cancer Res. 2011. Vol. 71. P. 4834-4845.
  8. Cucinotta F.A., Alp M., Sulzman F.M., Wang M. Space radiation risks to the central nervous system. Life Sci. Space Res. 2014. Vol. 2. P. 54-69.
  9. Ballesteros-Zebadúa P., Chavarria A., Celis M.A. et al. Radiation-induced neuroinflammation and radiation somnolence syndrome. CNS Neurol. Disord. Drug Targets. 2012. Vol. 11. P. 937-949.
  10. Kyrkanides S., Moore A.H., Olschowka J.A. et al. Cyclo­oxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury. Mol. Brain Res. 2002. Vol. 104. P. 159-169.
  11. Moore A.H., Olschowka J.A., Williams J.P. et al. Regulation of prostaglandin E2 synthesis after brain irradiation. Int. J. Radiat. Oncol. Biol. Phys. 2005. Vol. 62. P. 267-272.
  12. Hwang S.Y., Jung J.S., Kim T.H. et al. Ionizing radiation induces astrocyte gliosis through microglia activation. Neurobiol. Dis. 2006. Vol. 3. P. 457-467.
  13. Grigor'ev A.I., Krasavin E.A., Ostrovskij M.A. K ocenke riska biologicheskogo dejstviya galakticheskih tyazhyolyh ionov v usloviyah mezhplanetnogo polyota. Ros. fiziol. zhurn. im. I.M. Sechenova. 2013. Vol. 99. No. 3. P. 273-280. (In Russ.).
  14. Parihar V.K., Allen B., Tran K.K. et al. What happens to your brain on the way to Mars. Sci. Adv. 2015. Vol. 1. No. 4. e1400256. P. 1-6.
  15. Schindler M.K., Forbes M.E., Robbins M.E. et al. Aging- dependent changes in the radiation response of the adult rat brain. Int. J. Radiat. Oncol. Biol. Phys. 2008. Vol. 70. P. 826-834.
  16. Casadesus G., Shukitt-Hale B., Stellwagen H.M. et al. Hippocampal neurogenesis and PSA-NCAM expression following exposure to 56Fe particles mimics that seen during aging in rats. Exp. Geront. 2005. Vol. 40. P. 249-254.
  17. Joseph J.A., Hunt W.A., Rabin B.M., Dalton T.K. Possible “accelerated striatal aging” induced by 56Fe heavy particle irradiation: Implications for manned space flights. Radiat. Res. 1992. Vol. 130. P. 88-93.
  18. Forbes M.E., Paitsel M., Bourland J.D., Riddle D.R. Early-delayed, radiation-induced cognitive deficits in adult rats are hetero­ge­neous and age-dependent. Radiat. Res. 2014. Vol. 182. P. 60-71.
  19. Belokopytova K.V., Belov O.V., Kudrin V.S. et al. Raspredelenie monoaminov i ih metabolitov v strukturah golovnogo mozga krys v pozdnie sroki posle oblucheniya ionami 12C. Nejrohimiya. 2015. Vol. 32. No. 3. P. 243-251. (In Russ.).
  20. Belokopytova K.V., Belov O.V., Kudrin V.S. et al. Dinamika obmena monoaminov v strukturah golovnogo mozga krys v pozdnie sroki posle oblucheniya uskorennymi ionami ugleroda. Nejrohimiya. 2016. Vol. 33. No. 2. P. 147-155. (In Russ.).
  21. Rabin B.M., Joseph J.A., Shukitt-Hale B., McEwen J. Effects of exposure to heavy particles on a behavior mediated by the dopa­minergic system. Adv. Space Res. 2000. Vol. 25. P. 2065-2074.
  22. Hunt W.A., Joseph J.A. Rabin B.M. Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles. Adv. Space Res. 1989. Vol. 9. P. 333-336.
  23. Savchenko O.V. Status and prospects of new clinical methods of cancer diagnostics and treatment based on particle and ion beams available at JINR. Soobshch. Ob"ed. in-ta yader. issled. Dubna: OIYAI. 1996. 40 p. (In Russ.).
  24. Vagner R., Zorin V.P., Jiroushek P. et. al. Fiziko-dozimetricheskie izmereniya na gamma-apparate ROKUS-M. Soobshch. Ob"ed. in-ta yader. issled. Dubna: OIYAI. 1987. 13 p. (In Russ.).
  25. Matveeva M.I., Shtemberg A.S., Timoshenko G.N. et. al. Vliyanie oblucheniya ionami ugleroda 12S na obmen monoaminov v nekotoryh strukturah mozga krys. Nejrohimiya. 2013. Vol. 30. No. 4. P. 343-348. (In Russ.).
  26. Burke S.N., Barnes C.A. Neural plasticity in the ageing brain. Nat. Rev. Neurosci. 2006. Vol. 7. P. 30-40.
  27. Enzinger C., Fazekas F., Matthews P.M. et al. Risk factors for progression of brain atrophy in aging. Neurology. 2005. Vol. 64. P. 1704-1711.
  28. Olesen P.J., Guo X., Gustafson D. et al. A population-based study on the influence of brain atrophy on 20-year survival after age 85. Neurology. 2011. Vol. 76. P. 879-886.
  29. Barnes C.A. Normal aging: regionally specific changes in hippocampal synaptic transmission. Trends Neurosci. 1994. Vol. 17. P. 13-18.
  30. McEntee W.J., Crook T.M. Cholinergic function in the aged brain: implications for the treatment of memory impairments associated with aging. Behav. Pharmacol. 1992. Vol. 3. P. 327-336.
  31. Lamberty Y., Gower A.J. Age-related changes in spontaneous behavior and learning in NMRI mice from middle to old age. Physiol. Behav. 1992. Vol. 51. P. 81-88.
  32. Rasmussen T., Schliemann T., Sorenson J.C. et al. Memory impaired aged rats: No loss of principal hippocampal and subicular neurons. Neurobiol. Aging. 1996. Vol. 17. P. 143-147.
  33. Miyagawa H., Hasegawa M., Fukuta T. et al. Dissociation of impairment between spatial memory, and motor function and emotional behavior in aged rats. Behav. Brain. Res. 1998. Vol. 91. P. 73-81.
  34. Miguez J.M., Aldegunde M., Paz-Valinas L. et al. Selective changes in the contents of noradrenaline, dopamine and serotonin in rat brain areas during aging. J. Neural Transm. 1999. Vol. 106. P. 1089-1098.
  35. Darbin O., Risso J.-J., Rostain J.-C. Pressure induces striatal serotonin and dopamine increases: a simultaneous analysis in free moving microdialysed rats. Neuroscience Lett. 1997. Vol. 238. P. 69-72.

For citation: Belokopytova KV, Belov OV, Gaevsky VN, Narkevich VB, Kudrin VS, Krasavin EA, Bazyan A.S. Neuromediator Exchange Dynamics in Rats at Late Periods after Exposure to 60Co y-Rays. Medical Radiology and Radiation Safety. 2017;62(2):5-12. Russian. DOI: 10.12737/article_58f0b9572d7131.31568909

PDF (RUS) Full-text article (in Russian)