Problems of Radiation Medicine and Radiobiology

H. V. Kosiakova¹, S. А. Chumak², A. G. Berdyshev¹, I. Ya. Pinchuk², N. M. Hula¹, А. А. Chumak³

¹Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 9 Leontovich St.,
  Kyiv, 01054, Ukraine
²Institute of Psychiatry, Taras Shevchenko National University of Kyiv, 36 Lomonosov St.,
  Kyiv, 03022, Ukraine
³State Institution «National Research Center for Radiation Medicine of the National Academy of Medical
  Sciences of Ukraine», 53 Yuriy Ilyenko St., Kyiv, 04050, Ukraine

RADIATION DAMAGE OF THE NERVOUS SYSTEM AND ENDOCANABINOIDS

The review analyzes the change of the existing paradigm of high radioresistance of the nervous system according to the results of the study of neuropsychiatric disorders in in the aftermath of the Chornobyl accident in both early and remote post-accident period. The participation of the endocannabinoid system in ensuring homeostasis and pathology formation, potential possibilities of using cannabis drugs, agonists and antagonists of endocannabinoid receptors for the treatment of early and long-term effects of radiation are considered.
Key words: ionizing radiation, nervous system, endocannabinoid system.

Problems of Radiation Medicine and Radiobiology.
2020;25:75-89. doi: 10.33145/2304-8336-2020-25-75-89

full text

1. Yarmonenko SP. [Anti-radiation protection of the organism] (Moscow), Atomizdat, 1969. 246 p. Russian.
2. Kubashko AV, Ovsyannikova LM, Alekhina SM, Chumak SA, Nosach OV, Loganovsky KM, Chumak AA. [Peculiarities of biochemical changes in demyelinating and vascular diseases of the brain irradiated as a result of the Chernobyl disaster]. Ukrainian Neurological Journal. 2012;4:53-61. Ukrainian.
3. Yahyapour R, Amini P, Rezapour S, Cheki M, Rezaeyan A, Farhood B, et al. Radiation-induced inflammation and autoimmune diseases. Mil Med Res. 2018;5(1):9. doi: 10.1186/s40779-018-0156-7.
4. Portnov AA, Fedotov DD. [Mental disorders in radiation sickness]. Psychiatry (Mosсow) Meditsina; 1971. P. 279–282. Russian.
5. Loganovsky K, Kovalenko O, Chuprovska N, Antipchuk C, Bomko M, Napreyenko O, et al. Nervous system and psychosocial aspects. In: Serdiuk A., Bebeshko V., Bazyka D., Yamashita S., editors. Health effects of the Chernobyl accident: a quarter of century aftermath. Kyiv: DIA; 2011. p. 461-490.
6. Loganovsky K. N. Brain damage following exposure to low doses of ionizing radiation as a result of the Chernobyl accident. Clin Neuropsychiatry. 2012;9(5):203-204.
7. Loganovsky KN, Zdorenko LL. Intelligence deterioration following acute radiation sickness. Clin Neuropsychiatry. Journal of Treatment Evaluation. 2012;9(5):187-194.
8. Loganovsky KM. [Mental disorders under the action of ionizing radiation as a result of the Chornobyl disaster: neurophysiological mechanisms, unified clinical diagnosis, treatment] [dissertation]. Kyiv: Research Center of Radiation Medicine of the Academy of Medical Sciences of Ukraine; 2002. 462 p. Ukrainian.
9. Betlazar C, Middleton RJ, Banati RB, Liu GJ. The impact of high and low dose ionising radiation on the central nervous system. Redox Biol. 2016;9:144-156.
10. Nyagu AI, Loganovsky KN. Neuropsychiatric effects of ionizing radiation. Kyiv: Chornobylinterinform; 1998. 350 p. Russian.
11. Loganovsky KN, Vasilenko ZL. [Depression and ionizing radiation]. Probl Radiac Med Radiobiol. 2013;18:200-219. Russian.
12. Skvortsov VG, Soldatkin VA, Cherenkova IF. [On the relationship of the dose of ionizing radiation, reconstructed by the method of electronic paramagnetic resonance, with the characteristics of mental disorders in liquidators of the Chernobyl accident]. In: [Serial Murders and Social Aggression: What awaits us in the 21st century? Medical aspects of social aggression]: Proceedings of the 3rd International Scientific Conference; 2001 Sep18-21; Rostov-on-Don, Russia. Rostov-on-Don; 2001. p. 17-18. Russian.
13. Loganovsky KN, Zdanevich NA Cerebral basis of posttraumatic stress disorder following the Chernobyl disaster. CNS Spectr. 2013;18(2):95-102.
14. Loganovsky K, Havenaar JM, Tintle NL, Guey LT, Kotov R, Bromet EJ. The mental health of clean-up workers 18 years after the Chernobyl accident. Psychol Med. 2008;38(4):481-488.
15. Buzunov VA, Krasnikova LI., Pirogova EA, Tereshchenko VM, Voychulene YS [Epidemiological researches and an estimation of influence of small doses of ionizing radiation on development of not tumoral diseases at victims owing to Chornobyl accident]. Probl Radiac Med Radiobiol. 2007;13:56-66. Russian.
16. Krasnikova LI, Buzunov VA. [Risks of non-neoplastic pathology in participants in the clean-up workers of the Chornobyl accident according to in-depth clinical and epidemiological monitoring]. Probl Radiac Med Radiobiol. 2007;13:199-207. Russian.
17. Loganovsky KM, Chumak SA, Bomko MO. et al. [Cerebrovascular diseases and other brain lesions in victims of the Chornobyl disaster]. Journal of the National Academy of Medical Sciences of Ukraine. 2016;22(2):163-178. Ukrainian.
18. Loganovsky K, Bomko M, Chumak S, Loganovska T, Antypchuk K, Perchuk I, et al. Mental health and neuropsychiatric effects. In: Bazyka D, Sushko V, Chumak A, Chumak V, Yanovych L, editors. Health effects of Chornobyl accident – thirty years aftermath. Kyiv: DIA; 2016. p. 320-381.
19. Ivanov VK, Maksioutov MA, Chekin SY, Petrov A V, Biryukov A P, Kruglova ZG, et al. The risk of radiation induced cerebrovascular disease in Chernobyl emergency workers. Health Phys. 2006;90(3):199-207.
20. Buzunov VO, Kapustynska OA. Epidemiological studies of cerebrovascular diseaseof the population evacuated from the 30/km zone of the ChNPP at the age of 18/60 years. Analysis of the influence of internal ionizing radiation on the thyroid gland 131I. Probl Radiac Med Radiobiol. 2018;23:96-106.
21. Yaar I, Ron E, Modan B, Modan M, Peretz H. Long-term cerebral effects of small doses of X-іrradiation in childhood as manifested in adult visual evoked responses. Ann Neurol. 1980;8(3):261-268.
22. Buzunov VO, Loganovsky KN, Krasnikova LI, Bomko MO, Belyaev YM, Yaroshenko ZS, Domashevska TY. Social and psychological state of the Chornobyl cleanup workers. Risk factors for negative changes. Probl Radiac Med Radiobiol. 2016;21:106-118.
23. Loganovsky KM, Chumak SA, Bomko MO, Antipchuk KYu, Loganovskaya TK, Kolosinskaya OO et al. [Cerebrovascular diseases and other brain lesions in victims of the Chornobyl disaster]. Journal of the NAMSU. 2016;22(2):163-178. Ukrainian.
24. Loganovsky KN, Bomko MO, Abramenko IV, Kuts KV, Bilous NI, Masiuk SV, et al. Neuropsychobiological mechanisms of affective and cognitive disorders in the Chornobyl clean-up workers taking into account the specific gene polymorphisms. Probl Radiac Med Radiobiol. 2018;23:373-409.
25. Thirty years of the Chornobyl disaster: radiological and medical consequences: National Report of Ukraine. Kyiv; 2016. 177 p.
26. Loganovsky KN. Brain damage following exposure to low doses of ionizing radiation as a result of the Chernobyl accident. Clin Neuropsychiatry. 2012;9 (5):203-204.
27. Loganovsky K. Do low doses of ionizing radiation affect the human brain? [Electronic resource]. Data Science Journal. 2009;8:BR13–BR35. Available from: http://www.jstage.jst.go.jp/article/dsj/8/0/8_BR13/_article.
28. Ivanov VK. Late cancer and noncancer risks among Chernobyl emergency workers of Russia. Health Phys. 2007;93(5):470-479.
29. Buzunov V., Tereshchenko V., Krasnikova L. et al. Effects in the Chornobyl clean-up workers of 1986–1987. In: Serdiuk A., Bebeshko V., Bazyka D., Yamashita S., editors. Health effects of the Chernobyl accident: a quarter of century aftermath. Kyiv: DIA; 2011. p. 321-346.
30. Loganovsky K, Vasylenko Z. Depression and ionizing radiation. Probl Radiac Med Radiobiol. 2013;18:200-219.
31. Loganovsky K, Loganovskaja T. Cortical-limbic neurogenesis asymmetry as possible cerebral basis of brain laterality following exposure to ionizing radiation. Clin Neuropsychiatry. Journal of Treatment Evaluation. 2013;10(3-4):174.
32. Zhavoronkova LA, Belostotskyi A, Kholodova N, Kuptsova SV, Smegiryova I, Oknina L. [Disorders of higher mental functions and cognitive auditory evoked potentials in the liquidators of the Chornobyl accident]. S. Korsakov Journal Neurology and Psychiatry. 2012;5:62-69. Russian.
33. Kholodova NB, Zhavoronkova LA, Ryzhov BN, Kuznetsova GD. [Premature aging of the organism and features of its manifestation in the remote period after irradiation with small doses]. Uspekhi Gerontologii. 2007;20(4):48-55. Russian.
34. Loganovsky KN. Vegetative-vascular dystonia and osteoalgetic syndrome or chronic fatigue syndrome as a characteristic after-effect of radioecological disaster: the Chernobyl accident experience. Journal of Chronic Fatigue Syndrome. 2000;7(3):3-16.
35. Chumak A, Thevenon C, Gulaya N, Guichardant M, Margitich V, Bazyka D, et al. Monohydroxylated fatty acid content in peripheral blood mononuclear cells and immune status of people at long times after the Chernobyl accident. Radiat Res. 2001;156(5):476-487.
36. Loganovsky K, Perchuk I, Marazziti D. Clinical and psychophysiological data of the Chernobyl personnel working on transformation of the Object “Shelter” into an ecologically safe system. Clin Neuropsychiatry. Journal of Treatment Evaluation. 2015;12(3):57-63.
37. Loganovsky K., Perchuk I., Marazziti D. Workers on transformation of the shelter object of the Chernobyl nuclear power plant into an ecologically-safe system show qEEG abnormalities and cognitive dysfunctions: A follow–up study. World J Biol Psychiatry. 2015;23:1-8.
38. De Laurentiis A, Araujo HA, Rettori V. Role of the endocannabinoid system in the neuroendocrine responses to inflammation. Curr Pharm Des. 2014;20(29):4697-4706.
39. McPartland JM, Matias I, Di Marzo V, Glass M. Evolutionary origins of the endocannabinoid system. Gene. 2006;370:64-74.
40. Russo E. B. Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects. Br J Pharmacol. 2011;163(7):1344-1364.
41. Whiting PF, Wolff RF, Deshpande S, Di Nisio M, Duffy S, Hernandez AV, et al. Cannabinoids for medical use: a systematic review and meta-analysis. JAMA. 2015;313(24):2456-2473.
42. Herkenham M, Lynn AB, Little MD, Johnson MR, Melvin LS, de Costa BR, Rice KC. Cannabinoid receptor localization in brain. Proc Natl Acad Sci USA. 1990;87:1932-1936.
43. Derevyanko LP, Shelkovskiy MV, Atamaniuk NP, Frolova NO, Kosyakova GV, Mehed OF, et al. Experimental study of radiomodifying properties of N-stearoilethanolamine under a combined impact of ionizing radiation and stress. Probl Radiac Med Radiobiol. 2013;18:322-329.
44. Paradisi A, Oddi S, Maccarrone M. The endocannabinoid system in ageing: a new target for drug development. Curr Drug Targets. 2006;7(11):1539-1552.
45. Dyall SC. Interplay between N-3 and N-6 long-chain polyunsaturated fatty acids and the endocannabinoid system in brain protection and repair. Lipids. 2017;52(11):885-900.
46. Pagotto U, Marsicano G, Cota D, Lutz B, Pasquali R. The emerging role of the endocannabinoid system in endocrine regulation and energy balance. Endocr Rev. 2006;27(1):73-100. doi: 10.1210/er.2005-0009.
47. Rodriguez de Fonseca F, Del Arco I, Bermudez-Silva FJ, Bilbao A, Cippitelli A, Navarro M. The endocannabinoid system: physiology and pharmacology. Alcohol&Alcoholism. 2005;40(1):2-14.
48. Mackie K. Cannabinoid receptors: where they are and what they do? J Neuroendocrinol. 2008;20,Suppl 1:10-14.
49. Maccarrone M, Bab I, Biro T, Cabral GA, Dey SK, Di Marzo V, et al. Endocannabinoid signaling at the periphery: 50 years after THC. Trends Pharmacol Sci. 2015;36(5):277-296.
50. Kaur R, Ambwani SR, Singh S. Endocannabinoid system: a multi-facet therapeutic target. Curr Clin Pharmacol. 2016;11(2):110-117. doi:10.2174/1574884711666160418105339
51. Bronova I, Smith B, Aydogan B, Weichselbaum RR, Vemuri K, Erdelyi K, et al. Protection from radiation-induced pulmonary fibrosis by peripheral targeting of cannabinoid receptor-1. Am J Respir Cell Mol Biol. 2015;53(4):555-562.
52. Darmani NA, Janoyan JJ, Crim J, Ramirez J. Receptor mechanism and antiemetic activity of structurally-diverse cannabinoids against radiation-induced emesis in the least shrew. Eur J Pharmacol. 2007;563(1-3):187-196.
53. Donvito G, Nass SR, Wilkerson JL, Curry ZA, Schurman LD, Kinsey SG, et al. The endogenous cannabinoid system: a budding source of targets for treating inflammatory and neuropathic pain. Neuropsychopharmacology. 2018;43(1):52-79.
54. Chiurchiu V, van der Stelt M, Centonze D, Maccarrone M. The endocannabinoid system and its therapeutic exploitation in multiple sclerosis: Clues for other neuroinflammatory diseases. Prog Neurobiol. 2018;160:82-100.
55. Marcus DJ, Bedse G, Gaulden AD, Ryan JD, Kondev V, Winters ND, et al. Endocannabinoid signaling collapse mediates stress-induced amygdalo-cortical strengthening. Neuron. 2020;105(6):1062-1076. doi:10.1016/j.neuron.2019.12.024.
56. Hill MN, Campolongo P, Yehuda R, Patel S. Integrating endocannabinoid signaling and cannabinoids into the biology and treatment of posttraumatic stress disorder. Neuropsychopharmacology. 2018;43(1):80-102.
57. Bilyi DO, Nastina OM, Gabulavichene JM, Sidorenko GV, Bazyka OD, Bilaya VV, Kovalev OS. Factors of radiation and non-radiation nature and their influence on the course of coronary heart disease in participants in the aftermath of the Chornobyl accident. Probl Radiac Med And Radiobiol. 2014;14:213–222.
58. Ruiz de Azua I, Lutz B. Multiple endocannabinoid-mediated mechanisms in the regulation of energy homeostasis in brain and peripheral tissues. Cell Mol Life Sci. 2019;76(7):1341-63.
59. Pati S, Krishna S, Lee JH, Ross MK, de La Serre CB, Harn DA Jr, et al. Effects of high-fat diet and age on the blood lipidome and circulating endocannabinoids of female C57BL/6 mice/. Biochim Biophys Acta Mol Cell Biol Lipids. 2018;1863(1):26-39.
60. Chumak AA, Berdyshev AG, Kosyakova GV, Talko VV, Gula NM. Potential use of N-stearoylethanolamine in radiation medicine. Probl Radiac Med And Radiobiol. 2015;20:137-146.