EFFECTS OF INHALATION OF LOW DOSES OF RADON IN THE KRUSHINSKY-MOLODKINA RAT STRAIN AND STUDY OF VARIOUS BEHAVIORAL CHARACTERISTICS
Keywords:behavior, Na / K-ATPase, Oxidative Processes, radon
To study the effect of radon in balneotherapy, a group of experimental animals (multiple low doses in KM and epileptic Wistar rats were used) went through the procedure of inhalation of radon by the Tskaltubo mineral water pool, once daily, during 20 min, 10 days. In animals of the control groups, inhalation with radon was not used. After radon inhalation therapy with Tskaltubo mineral water, it was analyzed the absence or reduction of epileptic seizures. This research showed that Tskaltubo mineral water radon inhalation caused hormesis, absence or reduction of epileptic seizures. The result was stable during 6-12 months. Stabilization positively influenced oxidative stress levels, Na/K-ATF in epileptic rats. The result of our experiment gives us a stimulus to continue future research to find more specific neurochemical mechanisms participating in radon hormesis processes. Oxidative stress resulting from excessive free-radical release is likely implicated in the initiation and progression of epilepsy. An increase in active forms of oxygen or free radicals of oxygen is believed to play an important role in epileptic rats. To investigate the relationship between oxidative stress and memory impairment in epileptic mice, we determined the level of activity of antioxidant enzymes in blood plasma. The results showed that the level of lipid peroxidation in the plasma was significantly higher in epileptic rats than in control Wistar rats. Therefore, our study aimed to investigate the effects of radon inhalation on different forms of behavior in epileptic rats, both to positive and negative stimuli. As known from the literature, antioxidant therapies aimed at reducing oxidative stress have received considerable attention in epilepsy treatment. This article discusses various forms of behavior in KM rats as revealed by experiments. The KM rat strain differs from the Wistar rat strain in the nature of the locomotor activity, a higher level of exploratory activity, and increased emotionality. For rats of the KM rat strain, instability of behavioral reactions is characteristic, which manifests itself in all areas of their activity in the “open field” test. As for memory in epileptic rats, the behavior based on negative stimuli is not impaired in their psycho-neurological memory. Conditioned-reflex behavior developed on a positive stimulus, which we studied in a trestle-type maze, the obtained results showed that 10 epileptic rats complete the exit of this maze in 1 minute, already after 7 days without error. We have studied three sections of social environment awareness. It was determined that the time (p<0.001) and the number of contacts (p<0.001) were statistically significantly reduced among КM male rats. Decrease in indicators of social interaction: Group KM reliably spent less time in the compartment with animals (р<0.01) and spent more time near its cell. As a result of movement in the cross-maze, it was determined that KM rats spent more time in the closed arm, had more interrupted and rotated (tail-to-front) grooming than in the open arm, and also had a higher number of stand-ups than in the open arm, which is an indicator of its high anxiety. Inhalation of radon reduced oxidative stress in epileptic rats, and alleviated anxiety, together with definite memory improvement.
Aguilar B.L., Malkova L., N’Gouemo P., Forcelli P.A. Genetically epilepsy-prone rats display anxiety like behaviors and neuropsychiatric comorbidities of epilepsy. Front. Neurol. 2018. 9:476.
Becker, K. Is residential radon dangerous? In: The Effects of Low and Very low Doses of Ionizing Rad. on Human Health, Excerpta Medica Internat. Congr. Series 1203, 2000, 173-191 (ISBN 0-444-50513-x).
Beritashvili I.S. Vertebrate memory and its characteristics and origin. Metsniereba, Tbilisi, 1974. Beritashvili I.S. Vertebrate memory, its characteristics and origin. M. Nauka, 1974.
Chkadua G, Tsakadze L, Shioshvili L, Nozadze E, Na, K-atepase and CL-atepase regulation by dopamine. Georgian Medical News, 2021, 153-157.
Dondoladze K, Nikolaishvili M, Zurabashvili D. The effect of balneotherapy on the oxidative system and changes in anxiety behavior, enhanced by low doses of radon International J of Radiation Biology. 2021; 97(10):1461-69.
Algéo M.P., Bonheur B., Bubier J.A., Lu L., et al. QTL and systems genetics analysis of mouse grooming and behavioral responses to novelty in an open field. GenesBrainBehav. 2017;16(8):790–99.
Esman and Alpern H.P. Single trial; conditioning methodology and results mith nice. Psyxol.Rept. 1964; 14:731-740.
Falkenbach, A., et al., Radon progeny activity on skin and hair after speleotherapeutic radon exposure. J. Environm. Radioact. 2002; 62:217-223.
Guide for the Care and Use of Laboratory Animals. US Department of Health and Human Services (1985).
Henrikson, T., and H. D. Maillie, Radiation and Health, ISBN 0-415- 27162-2, 128, 2003
Jobe, P.C., Picchioni, A.L. and Lhin, L.Role of Norepinephrine in Audiogenic in the Rat. Journal of Pharmacology end Experimental Therapy. 1973; 184:1-10.
Kataoka T. Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation. Journal of Radiation Research. 2013; 54(4):587–596.
Krushinsky, L.V., Molodkina, L.N., Fless, D.A., Dobrokhotova, L.P., Steshenko, A.P.,Semiokhina, A.F., Zorina, Z.A. and Romanova, L.G. The Functional State of the Brain during Sonic Stimulation. In: Welch, B.L. and Welch, A.S., Eds., Physiological Effects of Noise, Plenum Press, New York, 1970; 151-158.
Lee, Y., Rodriguez, OC., Albanese, C., Santos, VR., Cortes de Oliveira, JA., Donatti, ALF., et all. Divergent brain changes in two audiogenic rat strains: a voxel-based morphometry and diffusion tensor imaging comparison of the genetically epilepsy prone rat (GEPR-3) and the Wistar Audiogenic Rat (WAR). 2018; 111:80-90.
Lomidze, G., Kasradze, S., Kvernadze, D., Okujava, N., Toidze, O., Hanneke, M., de Boer, Tarun Dua, & Josemir W. Sander. The prevalence and treatment gap of epilepsy in Tbilisi, Georgia, Epilepsy Research, 2012, 98(2-3):123-129.
Laetitia Prut, Catherine Belzung The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review, European Journal of Pharmacology. 2003; 463(1-3):28.
Fernando L, Silva A, Leonardo H. Rambo M, at all. The involvement of Na+, K+-ATPase activity and free radical generation in the susceptibility to pentylenetetrazol-induced seizures after experimental traumatic brain injury. J Neurol Sc 2011 Sep 15; 308(1-2):35-40.
Medel-Matus JS, Shin D, Sankar R, Mazarati A. Kindling epileptogenesis and panic-like behavior: Their bidirectional connection and contribution to epilepsy-associated depression. Epilepsy Behav EB 77:33-8. 10.1016/j.yebeh.2017.10.001
Nanobashvili Z, Chachua T, Bilanishvili I, Khizanishvili N. Peculiarities of the effects of stimulation of emotiogenic central structures under conditions of a kindling model of epilepsy, Neurophysiology 43 (4), 292-298.
Nikolaishvili M, Nanobashvili Z, Mitagvaria N. Radon Hormesiss in Epileptic Pathogenrsis and Predictors of Oxidative Stress. Georgian Medical News, 2021, 152-158.
Nikolashvili, M., Mchedluri, T., Museliani, T. Effect of Tskaltubo radon mineral waters on aggressive behaviour of animals and distribution of free amino acids in structures if the brain. saq. mecn. Acad. Mmacne, ser. Bboil. 2006; 32(1):119-123.
Nikolaishvili M, Nanobashvili Z, Mitagvaria N, Chkadua G, Museliani M, Assessment of Integrated Antioxidant Systems and Hormezis Effect of Radon in Experimental Studies. Journal of Biosciences and Medicines 2022, 10(3):212-227.
Ross, K.C., & Coleman, J.R. Developmental and genetic audiogenic seizure models: behavior and biological substrates. Neuroscience and Biobehavioral Reviews, 2000; 24:639-653.
Rosenkranz J. A., Johnston D. Dopaminergic regulation of neuronal excitability through modulation of Ih in layer V entorhinal cortex. J. Neurosci. 2006; 26:3229-3244.
Sakoda A, Ishimori Y, Kawabe A, Kataoka T, Hanamoto K, and Yamaoka K, “Physiologically based pharmacokinetic modeling of inhaled radon to calculate absorbed doses in mice, rats, and humans. Journal of Nuclear Science and Technology. 2010; 47(8):731-738.
Soto, J. Wirkung von Radon auf das Immunosystem, in H. G. Pratzel and J. Deetjen, Radon in der Kurortmedizin (ISBN 3-9894437-2-8), 1997, 103-113.
Sedlak, J., & Landsay, R. 1968. Biochem. 25, 192-205.
Yarmoshenko, IV Meta-analysis of radon and lung cancer case control studies. In: Proceedings of the 7th International Symposium, Natural Radiation Environment (NRE VII), Rhodes, May 2002, Elsevier Conf. Series, IP
Tevzadze G, Zhuravliova E, Barbakadze T, Shanshiashvili L, at all Gut neurotoxin p-cresol induces differential expression of GLUN2B and GLUN2A subunits of the NMDA receptor in the hippocampus and nucleus accumbens in healthy and audiogenic seizure-prone rats AIMS Neurosci. 2020; 7(1): 30-42.
Tevzadze G, Nanobashvili Z, Zhuravliova E, Bilanishvili I, Peculiarities of the effects of stimulation of emotiogenic central structures under conditions of a kindling model of epilepsy Neurophysiology 50 (6): 424-427.
Walf A.A. & Frye C.A. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nature Protocols. 2007; 2:322-328.