employee
Dubna, Moscow, Russian Federation
employee
Moscow, Russian Federation
employee
Moscow, Russian Federation
employee
Association of Medical Physicists of Russia (President)
employee
Russian Federation
employee
Russian Federation
employee
Moscow, Russian Federation
employee
Moscow, Russian Federation
UDK 61 Медицина. Охрана здоровья
GRNTI 76.03 Медико-биологические дисциплины
GRNTI 76.33 Гигиена и эпидемиология
OKSO 14.04.02 Ядерные физика и технологии
OKSO 31.06.2001 Клиническая медицина
OKSO 32.08.12 Эпидемиология
OKSO 31.08.08 Радиология
BBK 51 Социальная гигиена и организация здравоохранения. Гигиена. Эпидемиология
BBK 534 Общая диагностика
TBK 5708 Гигиена и санитария. Эпидемиология. Медицинская экология
TBK 5712 Медицинская биология. Гистология
TBK 5734 Медицинская радиология и рентгенология
TBK 6212 Радиоактивные элементы и изотопы. Радиохимия
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.
central nervous system, ionizing radiations, late effects, monoamines, metabolites
В последние годы накапливаются данные, свидетельствующие о высокой чувствительности отдельных элементов центральной нервной системы (ЦНС) к повреждающему действию ионизирующей радиации. Актуальность изучения разнообразных нейрорадиобиологических эффектов определяется рядом научно-практических задач, среди которых важное место занимает планирование сеансов радиотерапии и радиохирургии, обеспечение радиационной безопасности персонала, работающего в полях излучений физических установок, подготовка межпланетных пилотируемых полётов.
1. Grigor'evYu.G., Ushakov I.B., Krasavin E.A. i soavt. Kosmicheskaya radiobiologiya za 55let (k 50-letiyu GNC RF-IMBP RAN). - M.: Ekonomika. 2013. 303 s. Pp. 2-12 seeP. 11.
2. Yin E.,Nelson D.O., Coleman M.A. et al. Gene expression changes in mouse brain afterexposure to low-dose ionizing radiation // Int. J. Radiat. Biol. 2003. Vol. 79.P. 759-775.
3. SanchezM.C., Benitez A., Ortloff L., Green L.M. Alterations in glutamate uptake inNT2-derived neurons and astrocytes after exposure to gamma radiation // Radiat.Res. 2009. Vol. 171. P. 41-52.
4. BrittenR.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 spatiallearning ability of rats // Radiat. Res. 2012. Vol. 177. P. 146-151.
5. MonjeM.L., Mizumatsu S., Fike J.R., Palmer T.D. Irradiation induces neuralprecursor-cell dysfunction // Nat. Med. 2002. Vol. 8. P. 955-962.
6. MizumatsuS., Monje M.L., Morhardt D.R. et al. Extreme sensitivity of adult neurogenesisto low doses of x-irradiation // Cancer Res. 2003. Vol. 63. P. 4021-4027.
7. AcharyaM.M., Christie L.A., Lan M.L. et al. Human neural stem cell transplantationameliorates radiation-induced cognitive dysfunction // Cancer Res. 2011. Vol.71. P. 4834-4845.
8. CucinottaF.A., Alp M., Sulzman F.M., Wang M. Space radiation risks to the centralnervous system // Life Sci. Space Res. 2014. Vol. 2. P. 54-69.
9. Ballesteros-Zebadúa P., Chavarria A., Celis M.A. et al. Radiation-inducedneuroinflammation and radiation somnolence syndrome // CNS Neurol. Disord. DrugTargets. 2012. Vol. 11. P. 937-949.
10. KyrkanidesS., Moore A.H., Olschowka J.A. et al. Cyclooxygenase-2 modulates braininflammation-related gene expression in central nervous system radiation injury// Mol. Brain Res. 2002. Vol. 104. P. 159-169.
11. MooreA.H., Olschowka J.A., Williams J.P. et al. Regulation of prostaglandin E2synthesis after brain irradiation // Int. J. Radiat. Oncol. Biol. Phys. 2005.Vol. 62. P. 267-272.
12. HwangS.Y., Jung J.S., Kim T.H. et al. Ionizing radiation induces astrocyte gliosisthrough microglia activation // Neurobiol. Dis. 2006. Vol. 3. P. 457-467.
13. Grigor'evA.I., Krasavin E.A., Ostrovskij M.A. K ocenke riska biologicheskogo dejstviyagalakticheskih tyazhyolyh ionov v usloviyah mezhplanetnogo polyota // Ros.fiziol. zhurn. im. I.M. Sechenova. 2013. T. 99. No 3. S. 273-280. Pp. 14-18 seeP. 11.
14. PariharV.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. SchindlerM.K., Forbes M.E., Robbins M.E. et al. Aging-dependent changes in the radiationresponse of the adult rat brain // Int. J. Radiat. Oncol. Biol. Phys. 2008.Vol. 70. P. 826-834.
16. CasadesusG., Shukitt-Hale B., Stellwagen H.M. et al. Hippocampal neurogenesis andPSA-NCAM expression following exposure to 56Fe particles mimics that seenduring aging in rats // Exp. Geront. 2005. Vol. 40. P. 249-254.
17. JosephJ.A., Hunt W.A., Rabin B.M., Dalton T.K. Possible “accelerated striatal aging”induced by 56Fe heavy particle irradiation: Implications for manned spaceflights // Radiat. Res. 1992. Vol. 130. P. 88-93.
18. ForbesM.E., Paitsel M., Bourland J.D., Riddle D.R. Early-delayed, radiation-inducedcognitive deficits in adult rats are heterogeneous and age-dependent // Radiat.Res. 2014. Vol. 182. P. 60-71.
19. BelokopytovaK.V., Belov O.V., Kudrin V.S. i soavt. Raspredelenie monoaminov i ihmetabolitov v strukturah golovnogo mozga krys v pozdnie sroki posle oblucheniyaionami 12C // Nejrohimiya. 2015. T. 32. No 3. S. 243-251.
20. BelokopytovaK.V., Belov O.V., Kudrin V.S. i soavt. Dinamika obmena monoaminov v strukturahgolovnogo mozga krys v pozdnie sroki posle oblucheniya uskorennymi ionamiugleroda// Nejrohimiya. 2016. T. 33. No 2. S. 147-155. Pp. 21-23 see P. 11.
21. RabinB.M., Joseph J.A., Shukitt-Hale B., McEwen J. Effects of exposure to heavyparticles on a behavior mediated by the dopaminergic system // Adv. Space Res.2000. Vol. 25. P. 2065-2074.
22. HuntW.A., Joseph J.A. Rabin B.M. Behavioral and neurochemical abnormalities afterexposure to low doses of high-energy iron particles // Adv. Space Res. 1989.Vol. 9. P. 333-336.
23. SavchenkoO.V. Status and prospects of new clinical methods of cancer diagnostics andtreatment based on particle and ion beams available at JINR. Сообщ. Объед.ин-та ядер. исслед. - Дубна: ОИЯИ. 1996. 40 c.
24. VagnerR., Zorin V.P., Jiroushek P. i soavt. Fiziko-dozimetricheskie izmereniya nagamma-apparate ROKUS-M. Soobshch. Ob"ed. in-ta yader. issled. - Dubna:OIYAI. 1987. 13 s.
25. MatveevaM.I., SHtemberg A.S., Timoshenko G.N. i soavt. Vliyanie oblucheniya ionamiugleroda 12S na obmen monoaminov v nekotoryh strukturah mozga krys //Nejrohimiya. 2013. T. 30. No 4. S. 343-348. Pp. 26-35 see P. 11.
26. BurkeS.N., Barnes C.A. Neural plasticity in the ageing brain // Nat. Rev. Neurosci.2006. Vol. 7. P. 30-40.
27. EnzingerC., Fazekas F., Matthews P.M. et al. Risk factors for progression of brainatrophy in aging // Neurology. 2005. Vol. 64. P. 1704-1711.
28. OlesenP.J., Guo X., Gustafson D. et al. A population-based study on the influence ofbrain atrophy on 20-year survival after age 85 // Neurology. 2011. Vol. 76. P.879-886.
29. BarnesC.A. Normal aging: regionally specific changes in hippocampal synaptictransmission // Trends Neurosci. 1994. Vol. 17. P. 13-18.
30. McEnteeW.J., Crook T.M. Cholinergic function in the aged brain: implications for thetreatment of memory impairments associated with aging // Behav. Pharmacol.1992. Vol. 3. P. 327-336.
31. LambertyY., Gower A.J. Age-related changes in spontaneous behavior and learning in NMRImice from middle to old age // Physiol. Behav. 1992. Vol. 51. P. 81-88.
32. RasmussenT., Schliemann T., Sorenson J.C. et al. Memory impaired aged rats: No loss ofprincipal hippocampal and subicular neurons // Neurobiol. Aging. 1996. Vol. 17.P. 143-147.
33. MiyagawaH., Hasegawa M., Fukuta T. et al. Dissociation of impairment between spatialmemory, and motor function and emotional behavior in aged rats // Behav. Brain.Res. 1998. Vol. 91. P. 73-81.
34. MiguezJ.M., Aldegunde M., Paz-Valinas L. et al. Selective changes in the contents ofnoradrenaline, dopamine and serotonin in rat brain areas during aging // J.Neural Transm. 1999. Vol. 106. P. 1089-1098.
35. DarbinO., Risso J.-J., Rostain J.-C. Pressure induces striatal serotonin and dopamineincreases: a simultaneous analysis in free moving microdialysed rats //Neuroscience Lett. 1997. Vol. 238. P. 69-72.
