Dynamics of changes in the content of thyroid hormones and some neurotransmitters in brain of rats with experimental Alzheimer’s disease

Динамика изменения содержания тиреоидных гормонов и некоторых нейромедиаторов в коре головного мозга крыс с экспериментальной болезнью Альцгеймера
Tatiana Gorbach 1, Galina Gubina-Vakyulyk 2, Oksana Nakonechna 1, Anton Tkachenko 1
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1 Department of biochemistry, Kharkiv National Medical University, Kharkiv, Ukraine
2 Department of Pathological anatomy, Kharkiv National Medical University, Kharkiv, Ukraine
J CLIN MED KAZ, Volume 4, Issue 46, pp. 26-32. https://doi.org/10.23950/1812-2892-JCMK-00472
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ABSTRACT

Objective: Alzheimer's disease is one of the most common neurodegenerative diseases, and mechanisms of its development have been studied for many years. The aim of the research was to study the content of thyroid-stimulating hormone (TSH), thyroid hormones and tau protein in the blood serum, as well as the content of thyroid hormones and some neurotransmitters in the cerebral cortex in the dynamics of experimental Alzheimer’s disease in rats.
Materials and methods. The experiment was performed on 45 WAG rats, which were divided into 3 groups. The first group was the control one. Animals from the second and third groups were intraperitoneally administered with scopolamine for 14 and 27 days, which led to the development of Alzheimer's disease. Brain homogenate was prepared. Concentrations of T3, T4 in blood serum and homogenates of the cerebral cortex, as well as TSH and tau protein in serum, were determined by ELISA. Determination of the content of neurotransmitter amino acids (aspartate and glutamate) was carried out by thin-layer chromatography. The content of dopamine and norepinephrine in the cerebral cortex homogenate was determined by column chromatography, and acetylcholine levels were measured by spectrophotometry. Morphological examination included staining of brain tissue with congo-rot + hematoxylin.
Results. It was established that in cerebral cortex homogenates of rats with experimental Alzheimer’s disease the T3 content was reduced, and T4 levels were similar to rats of the control group, which in combination with the normal concentration of thyroid hormones in blood serum indicates the development of local hypothyroidism in the cerebral cortex. In rats with Alzheimer's disease, glutamic and aspartic acid levels were increased against the background of GABA reduction. There was also a decrease in the levels of noradrenaline and dopamine in the cerebral cortex homogenates, which contributes to the abnormal energy metabolism and impaired cognitive functions. Morphological study demonstrated the presence of congophilic masses in the brain tissue and in the walls of small arteries with the development of brain atrophy.
Conclusions. Alzheimer's disease caused by the administration of scopalamine is characterized by the development of local hypothyroidism in the cerebral cortex, an increase in the level of glutamic and aspartic acids with a decrease in GABA, a decrease in the level of dopamine and norepinephrine in the cerebral cortex.
Keywords: Alzheimer’s disease, thyroid hormones, neurotransmitters, rats

CITATION

Gorbach T, Gubina-Vakyulyk G, Nakonechna O, Tkachenko A. Dynamics of changes in the content of thyroid hormones and some neurotransmitters in brain of rats with experimental Alzheimer’s disease. Journal of Clinical Medicine of Kazakhstan. 2017;4(46):26-32. https://doi.org/10.23950/1812-2892-JCMK-00472

REFERENCES

  • Kumar A, Singh A, Ekavali. A review on Alzheimer’s disease pathophysiology and its management: an update, Pharmacol Rep. 2015;67(2):195-203.
  • Taylor CA, Greenlund SF, McGuire LC et al. Deaths from Alzheimer’s disease — United States, 1999–2014. Weekly. 2017;66(20):521-526.
  • Zagrebin V.L., Antoshkin O.N., Fedorova O.V., et al. Patogeneticheskie mehanizmy razvitija bolezni Al’cgejmera (Pathogenetic mechanisms of the developmet of Alzheimer’s disease) [in Russian]. Vestnik VolGMU. 2016;3(59):7-12.
  • Craig LA, Hong NS, McDonald RJ. Revisiting the cholinergic hypothesis in the development of Alzheimer’s disease. Neurosci Biobehav Rev. 2011;35(6):1397-409.
  • Hardy JA, Higgins GA. Alzheimer’s disease: the amyloid cascade hypothesis. Science.1992; 256(5054):184-5.
  • Selkoe DJ, Hardy J. The amyloid hypothesis of Alzheimer’s disease at 25 years. EMBO Mol Med. 2016;8(6):595-608.
  • Maccioni RB, Farías G, Morales I et al. The revitalized tau hypothesis on Alzheimer’s disease. Arch Med Res. 2010;41(3):226-31.
  • Tan ZS, Vasan RS. Thyroid function and Alzheimer’s disease. J Alzheimers Dis. 2009;16(3):503-7.
  • Danysz W, Parsons CG. Alzheimer’s disease, β-amyloid, glutamate, NMDA receptors and memantine--searching for the connections. Br J Pharmacol. 2012;167(2):324-52.
  • Martorana A, Koch G. Is dopamine involved in Alzheimer’s disease? Front Aging Neurosci. 2014;6:252.
  • Mironova A.N. Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. Chast’ pervaja. (Manual for carrying out preclinical researches of drugs. Part 1) [in Russian], Moscow: Grif i K; 2012.
  • Dejko RD, Shtrigol’ SJu, Gorbach TV et al. Nootropnі vlastivostі tetrapeptidu Acetyl-(D-Lys)-Lys-Arg-Arg-Amide (KK-1) na modelі hvorobi Al’cgejmera u shhurіv, zumovlenoї hronіchnim vvedennjam skopolamіnu (Nootropic properties of a tetrapeptide Acetyl-(D-Lys)-Lys-Arg-Arg-Amide (КК-1) using a model of Alzheimer’s disease in rats caused by chronic scopolamine intake) [in Ukrainian]. Klіnіchna farmacіja. 2016;20 (4):52-761.
  • Drozdov N.S., Materanskaja N.P. Praktikum po biologicheskoj himii (Practical guide on biochemistry) [in Russian], Moscow:Vysshaja shkola;, 1998. 296 p. 
  • Trubicyna I.E., Drozdov V.N., Lazebnik L.B. et al. Pat. 2256920 Rossijskaja Federacija MPK G 01 N 33/50 Sposob opredelenija acetilholina (The way of acetylcholine determination) – 2003127761/15. Zajavl.: 27.03.2005. Opubl.: 20.07.2005 [in Russian]. – Bul. 20. – 15 p.
  • Atack C, Magnusson T. A procedure for the isolation of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from the same tissue sample using a single column of strongly acidic cation exchange resin. Acta Pharmacol Toxicol (Copenh). 1978;41(1):35-57.
  • Sarkisov D.S., Perov Ju.L. Mikroskopicheskaja tehnika: rukovodstvo dlja vrachej i laborantov (Microscopic technique: a guide for physicians and laboratory assistants) [in Russian], RAMN; Medicina; 1996. 544 p.
  • Mendes-de-Aguiar CB, Alchini R, Decker H et al. Thyroid hormone increases astrocytic glutamate uptake and protects astrocytes and neurons against glutamate toxicity. J. Neurosci. Res. 2008;86(14):3117-25.
  • Bauer M, Heinz A, Whybrow PC. Thyroid hormones, serotonin and mood: of synergy and significance in the adult brain. Mol Psychiatry. 2002;7(2):140-56.
  • Atamna H, Frey WH. Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer’s disease. Mitochondrion. 2007;7(5):297-310.
  • Kim JY, Kim N, Zheng Z et al. The 70 kDa heat shock protein protects against experimental traumatic brain injury. Neurobiol Dis. 2013;58:289-95.
  • Gorodetskaya IV, Bozhko AP, Bakhtina LY et al. Role of thyroid hormones in stress-induced synthesis of heat-shock proteins in the myocardium. Bul of Exp Biol and Med. 2000;130(12):1138-1140.
  • Hshieh TT, Fong TG, Marcantonio ER et al. Cholinergic deficiency hypothesis in delirium: a synthesis of current evidence. Bull Ex J Gerontol A Biol Sci Med Sci. 2008;63(7):764-72.
  • Lai TW, Zhang S, Wang YT. Excitotoxicity and stroke: identifying novel targets for neuroprotection. Prog Neurobiol. 2014;115:157-88.
  • Van de Ven AC, Muntjewerff JW, Netea-Maier RT et al. Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression. Acta Psychiatrica Scandinavica. 2012;126 (5):337-384.
  • Santos NC, Costa P, Ruano D et al. Revisiting thyroid hormones in schizophrenia. J. Thyroid Res. 2012:569147 doi:10.1155/2012/569147