ISSN 2415-3060 (print), ISSN 2522-4972 (online)
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УЖМБС 2018, 3(5): 306–310
https://doi.org/10.26693/jmbs03.05.306
Biology

Anxiolytic Effect of Thyroid Hormones

Rodinsky A. G. 1, Demchenko A. N. 1, Kondratyeva O. Yu. 1, Rodinskaya G. A. 1, Kirichenko S. V. 2
Abstract

Higher brain functions are determined by the activity of the neurohumoral regulation. Among the hormones that affect the cognitive activity of the central nervous system, an important role belongs to thyroid hormones. The purpose of the study was to establish and clarify the role of neurotransmitter amino acids in implementing the effect of thyroid hormones (TH) on the formation of psycho-emotional status of young rats. Material and methods. The experiments were performed on the young white rats of the Wistar line. The hyperthyroid condition was modeled by administration of L-thyroxine tablets («Berlin-Chemie AJ», Germany) with food in powdered form for two weeks in doses that gradually increased, due to the inactivation of exogenous thyroxine. At the beginning of the experiment, the dose of the drug was higher than the daily production of thyroxine (3-5 mcg / animal) and was 10 mcg / day. Daily concentration of thyroxine was increased by 5mcg in comparison with the previous one. The hypothyroid condition was created by administering mercazolil in a dose of 10 mg / kg for two weeks. The probability of the established model was confirmed by determination of concentrations of thyroxine (T4) and thyroid-stimulating hormone (TSH) in blood plasma of the experimental rats and assessment of the clinical status of animals: body weight, heart rate, mobility, excitability, and emotional. Results and discussion. The study of the behavior of young rats in the elevated plus maze (EPM) showed that the condition of hyperthyroidism caused an increase in the presence of animals in the light part of the labyrinth. In particular, the number of transitions in the light of sleeves increased by 87.7%, and the duration of their presence in them increased at 2.6 times. At the same time, the index of the vegetative component of the emotional reaction decreased: the number of bolus of defecation on average was 0.43±0.04, which was 66.7% less than control. These changes in behavioral activity indicate a significant anxiolytic effect. In the background of chronic stress, the hyperthyroid condition was characterized by a significant depressing effect. In particular, there was an increase in the length of stay in the light compartments of the labyrinth at 3,6 times, which was supplemented by a decrease of activities in dark corridors by 36,2%. The number of racks also decreased by 49.8% relative to control. Acute stress caused even more significant inhibition of behavioral activity: the number of transitions in dark sleeves decreased by 35%, stanchions – by 26.2%, bolus of defecation – by 52.8%, hanging – by 20.5%. And only one indicator, as in the case of "hyperthyroidism" and with the combination "hyperthyroidism + chronic stress" remained increased by 2.3 times – the duration of stay in light sleeves, which is obviously due to anxiolytic effect. Investigation of the level of free amino acids of the neurotransmitter spectrum in the neocortex revealed an increase in the serotonin and glycine content by 33% and 17.5%. In contrast to hyperthyroidism, the state of hypothyroidism was accompanied by a significant decrease in behavioral activity, which increased doubled in comparison with acute stress – by 78.5%, relative to control (p<0.05). Conclusions. Thus, unidirectional behavioral changes, the level of free neurotransmitter amino acids of inhibitory nature (increasing the content of GABA and glycine by 18 % at 51 % of rats) and the activity of NO-synthase may indicate an advantage in the neocortex of the depressant effect. The latter may be due to the mechanism of hyperthyroidism protective braking against the background of hypothyroidism with the mechanism of direct inhibition, as a result of reduced metabolism.

Keywords: experimental hypo-hyperthyroidism, anxiolytic effect, neurotransmitter amino acids

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References
  1. Ahmed RG. Hypothyroidism and brain developmental players. Thyroid Res. 2015; 8 (2): 96-104. https://www.ncbi.nlm.nih.gov/pmc/articles/4397876. https://www.ncbi.nlm.nih.gov/pubmed/25878727. https://doi.org/10.1186/s13044-015-0013-7
  2. Göbel A, Heldmann M, Göttlich M, Dirk AL, Brabant G, Münte T F. Effect of Experimental Thyrotoxicosis on Brain Gray Matter: A Voxel-Based Morphometry Study. Eur Thyroid J. 2015 Sep; 4 (1): 113–8. https://www.ncbi.nlm.nih.gov/pubmed/26601082. https://www.ncbi.nlm.nih.gov/pmc/articles/4640290. https://doi.org/10.1159/000398793
  3. Rovet JF. The role of thyroid hormones for brain development and cognitive function. Endocr Dev. 2014; 26: 26-43. https://www.ncbi.nlm.nih.gov/pubmed/25231442. https://doi.org/10.1159/000363153.
  4. Darras VM, Houbrechts AM, Van Herck SL. Intracellular thyroid hormone metabolism as a local regulator of nuclear thyroid hormone receptor-mediated impact on vertebrate development. Biochim Biophys Acta. 2015 Feb; 1849 (2): 130-41. https://www.ncbi.nlm.nih.gov/pubmed/24844179. https://doi.org/10.1016/j.bbagrm.2014.05.004
  5. Rodrigues TB, Ceballos A, Grijota-Martínez C, Nuñez B, Refetoff S, Cerdán S, Morte B, Bernal J. Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter Slc16a2 (Mct8). PLoS One. 2013; 8 (10): e74621. Published online 2013 Oct 1. https://www.ncbi.nlm.nih.gov/pubmed/24098341. https://www.ncbi.nlm.nih.gov/pmc/articles/3788064. https://doi.org/10.1371/journal.pone.0074621
  6. Sapronov NS, Fedotova YO. Gormony gipotalamo-gipofizarno-tireoidnoy sistemyi i mozg. SPb: Lan, 2002. 184 s. [Russian]
  7. Buresh Y, Bureshova O, Hyuston D. Metodiki i osnovnyie eksperimenty po izucheniyu mozga i povedeniya. Moskva: Vyсsh shk, 1991. 399 s. [Russian]
  8. Chekman IS, Belenichev IF, Nagorna OO, Gorchakova NA, i dr. Doklinicheskoe izuchenie spetsificheskoy aktivnosti potentsialnyh sredstv pervichnoy i vtorichnoy neyroprotektsii. Metod rekomend. GETs MZ Ukrainyi. Kiev: OOO «Izdatelstvo «Yuston», 2016. 82 s. [Russian]
  9. Kokunin VA. Statisticheskaya obrabotka danych pri malom chisle opitov. Ukr biochim Jurnal. 1975; 47 (6): 776-91. [Russian]
  10. Nadorova AV, Kolik LG, Klodt PM, Narkevich VB, Naplekova PL, Kozlovskaya MM, i dr. Sootnoshenie anksioliticheskogo deystviya selanka i urovnya serotonina v otdelnyh strukturah mozga pri modelirovanii alkogolnoy abstinentsii u kryis. Neyrohim. 2014; 31 (2): 141–7. https://doi.org/10.7868/S1027813314020083 [Russian]
  11. Tyurenkov IN, Bagmetova VV, Robertus AI, Vasileva EV, Kovalev GI. Izuchenie GAMK- ergicheskih mehanizmov neyropsihotropnogo deystviya neyroglutama. Neyrohim. 2015; 32 (2): 140-52. https://doi.org/10.7868/S1027813315010136 [Russian]
  12. Bagatolli LA, Ipsen JH, Simonsen AC, Mouritsen OG. An outlook on organization of lipids in membranes: Searching for a realistic connection with the organization of biological membranes. Progress in Lipid Research. 2012; 49: 378-89. https://www.ncbi.nlm.nih.gov/pubmed/20478336. https://doi.org/10.1016/j.plipres.2010.05.001
  13. Carhart-Harris RL, Nutt DJ. Serotonin and brain function: a tale of two receptors. J Psychopharmacol. 2017 Sep; 31 (9): 1091–200. https://www.ncbi.nlm.nih.gov/pubmed/28858536. https://www.ncbi.nlm.nih.gov/pmc/articles/5606297. https://doi.org/10.1177/0269881117725915
  14. Grinkevich LN, Vorobeva OV. Serotonin i neyropeptid FMRFamid igrayut protivopolozhnuyu rol v regulyatsii epigeneticheskih protsessov, vovlechennyih v formirovanie dolgovremennoy pamyati. Vavilov J genetiki i selektsii. 2016; 20 (2): 262-8. https://doi.org/10.18699/VJ16.128 [Russian]