Oğuzhan Ekin EFE, Selda EMRE AYDINGÖZ, Karl Michael LUX, Eda ÖZER, Ayşegül SÜZER, Meral TUNCER

Metimazol ile Oluşturulan Sıçan Hipotiroidi Modelinde Kognitif Fonksiyonlar, Anksiyete ve Depresyon Benzeri Davranışların Değerlendirilmesi: Pilot Çalışma

Hipertiroidizm tedavisinde yaygın olarak kullanılan metimazol, deneysel çalışmalarda geçici hipotiroidizm modeli oluşturmak için kullanılmaktadır. Çalışmamızda metimazol ile oluşturulan sıçan hipotiroidi modelinde kognitif fonksiyonların değerlendirilmesi ve hipotiroidinin anksiyete ve depresyon benzeri davranışlar üzerine etkisinin belirlenmesi amaçlanmıştır. Oniki adet erişkin dişi/erkek Wistar sıçan (250-300 g) iki gruba ayrılarak bir gruba 4 hafta süre ile içme suyu içinde %0,02 metimazol verilerek hipotiroidizm oluşturulmuş, diğer gruba normal içme suyu verilmiştir. Dört hafta sonunda, Morris su labirenti, yükseltilmiş artı labirent, kuyruk suspansiyon testi, pasif sakınma testi uygulanmıştır. Metimazol kesildikten 8 hafta sonra serum serbest T4 ve TSH düzeyleri ölçülmüş ve tiroid dokusu histopatolojik olarak değerlendirilmiştir. Morris su labirenti testinde sadece 1. günde gruplar arasında anlamlı fark izlenmiştir (p

Anahtar Kelimeler:

Hipotiroidizm, Kognitif fonksiyon, Sıçan, Metimazol

Evaluation of Cognitive Functions, Anxiety- and Depression-Like Behaviours in Methimazole-Induced Rat Hypothyroidism Model: A Pilot Study

Methimazole, a widely used agent in the treatment of hyperthyroidism, is also used to induce hypothyroidism in experimental studies. In this study, we aimed to evaluate cognitive functions and anxiety- and depression-like behaviours in a methimazole-induced rat hypothyroidism model. Twelve adult female/male Wistar rats (250-300 g) were randomly divided into two groups, one of which was given 0.02% methimazole in drinking water for 4 weeks, as the other group was given normal water. After 4 weeks, Morris water maze, elevated plus maze, tail suspension test, passive avoidance test was applied. Serum free T4 and TSH levels were measured 8 weeks after discontinuation of methimazole, and thyroid tissue was evaluated histopathologically. In the Morris water maze test, a significant difference was observed between the groups only on the 1st day (p

Keywords:

Hypothyroidism, Cognitive Function, Rat, Methimazole,

PDF

___

1.Vallortigara J, Alfos S, Micheau J et al. T3 administration in adult hypothyroid mice modulates expression of proteins involved in striatal synaptic plasticity and improves motorbehavior. Neurobiol Dis. 2008;31(3):378-85.
2.Boelaert K, Franklyn JA. Thyroid hormone in health anddisease. J Endocrinol. 2005;187(1):1-15.
3.Constant EL, Adam S, Seron X, et al. Anxiety and depression, attention, and executive functions in hypothyroidism. J Int Neuropsychol Soc. 2005;11(5):535-44.
4.Gulseren S, Gulseren L, Hekimsoy Z, et al. Depression, anxiety, health-related quality of life, and disability in patients with overt and subclinical thyroid dysfunction. Arch Med Res. 2006;37(1):133-9.
5.Miller KJ, Parsons TD, Whybrow PC, van Herle K, Rasgon N,van Herle A, Martinez D, Silverman DH, Bauer M. Memory improvement with treatment of hypothyroidism. Int J Neurosci. 2006;116(8):895-906.
6.Oziol L, Faure P, Bertrand N, et al. Inhibition of in vitro macrophage-induced low density lipoprotein oxidation by thyroid compounds. J Endocrinol. 2003;177(1):137-46.
7.Torun AN, Kulaksizoglu S, Kulaksizoglu M, et al. Serum total antioxidant status and lipid peroxidation markermalondialdehyde levels in overt and subclinical hypothyroidism. Clin Endocrinol (Oxf). 2009;70(3):469-74.
8.Psarra AM, Solakidi S, Sekeris CE. The mitochondrion as a primary site of action of steroid and thyroid hormones: presence and action of steroid and thyroid hormone receptors inmitochondria of animal cells. Mol Cell Endocrinol. 2006;246(1-2):21-33.
9.Rahaman SO, Ghosh S, Mohanakumar KP, et al.Hypothyroidism in the developing rat brain is associated with marked oxidative stress and aberrant intraneuronal accumulation of neurofilaments. Neurosci Res. 2001;40(3):273-9.
10.Pérez-Severiano F, Escalante B, Vergara P, Ríos C, Segovia J. Age-dependent changes in nitric oxide synthase activity andprotein expression in striata of mice transgenic for the Huntington's disease mutation. Brain Res. 2002;951(1):36-42.
11.Işman CA, Yeğen BC, Alican I. Methimazole-inducedhypothyroidism in rats ameliorates oxidative injury in experimental colitis. J Endocrinol. 2003;177(3):471-6.
12.Hayat NQ, Tahir M, Munir B, et al. Effect of methimazole-induced hypothyroidism on histological characteristics of parotid gland of albino rat. J Ayub Med Coll Abbottabad. 2010;22(3):22-7.
13.Desouza LA, Ladiwala U, Daniel SM, Agashe S, Vaidya RA,Vaidya VA. Thyroid hormone regulates hippocampal neurogenesis in the adult rat brain. Mol Cell Neurosci.2005;29(3):414-26.
14.Cortés C, Eugenin E, Aliaga E, et al. Hypothyroidism in theadult rat causes incremental changes in brain-derived neurotrophic factor, neuronal and astrocyte apoptosis, gliosis, and deterioration of postsynaptic density. Thyroid. 2012;22(9):951-63.
15.Salas-Lucia F, Pacheco-Torres J, González-Granero S, García-Verdugo JM, Berbel P. Transient hypothyroidism during lactation alters the development of the corpus callosum in rats. an in vivo magnetic resonance ımage and electron microscopy study. Front Neuroanat. 2020;14:33.
16.Mishra J, Vishwakarma J, Malik R, et al. Hypothyroidism induces ınterleukin-1-dependent autophagy mechanism as a key mediator of hippocampal neuronal apoptosis and cognitive decline in postnatal rats. Mol Neurobiol. 2021;58(3):1196-211.
17.O'Hare E, Kim EM, Page D, Reid R. Effects of thyroxinetreatment on histology and behavior using the methimazolemodel of congenital hypothyroidism in the rat. Neuroscience. 2015;285:128-38.
18.Nunez J. Morris water maze experiment. J Vis Exp. 2008;(19):897.
19.Komada M, Takao K, Miyakawa T. Elevated plus maze formice. J Vis Exp. 2008;(22):1088.
20.Steru L, Chermat R, Thierry B, et al. The tail suspension test: anew method for screening antidepressants in mice. Psychopharmacology (Berl). 1985;85(3):367-70.
21.Rodriguez A, Zhang H, Klaminder J, et al. ToxTrac: a fast and robust software for tracking organisms. Met Ecol Evol. 2018;9:460-4.
22.Zhou XL, Han Y, Mail WJ, Liu J, Wang H, Feng L, Gao L,Zhao JJ. Different doses and Rroutes of administration of methimazole affect thyroid status in methimazole-induced hypothyroidism in rats. West Indian Med J. 2015;7:65(1):93-97.
23.Cakic-Milosevic M, Korac A, Davidovic V. Methimazole-induced hypothyroidism in rats: Effects on body weight and histological characteristics of thyroid gland. Jugoslovenska Medicinska Biohemija. 2004; 23: 143-147.
24.Hosseini M, Dastghaib SS, Rafatpanah H, Hadjzadeh MA, Nahrevanian H, Farrokhi I. Nitric oxide contributes to learning and memory deficits observed in hypothyroid rats during neonatal and juvenile growth. Clinics (Sao Paulo).2010;65(11):1175-81.
25.van Wijk N, Rijntjes E, van de Heijning BJ. Perinatal and chronic hypothyroidism impair behavioural development inmale and female rats. Exp Physiol. 2008;93(11):1199-209.
26.Xu YX, Sun Y, Cheng J, et al. Genetic difference of hypothyroidism-ınduced cognitive dysfunction in C57BL/6j and 129/Sv mice. Neurochem Res. 2019;44(8):1999-2006.
27.Chaalal A, Poirier R, Blum D, et al. PTU-induced hypothyroidism in rats leads to several early neuropathological signs of Alzheimer's disease in the hippocampus and spatial memory impairments. Hippocampus. 2014;24(11):1381-93.
28.Yu D, Zhou H, Yang Y, et al. The bidirectional effects ofhypothyroidism and hyperthyroidism on anxiety- and depression-like behaviors in rats. Horm Behav. 2015;69:106-15.
29.Jin Z, Ling J, Yu J, He M, Ni P, Zhang F, Wang Y. Serotonin2A receptor function and depression-like behavior in rats model of hypothyroidism. Exp Brain Res. 2021;239(8):2435-444.
30.Lee J, Yi S, Kang YE, et al. Morphological and functional changes in the thyroid follicles of the aged murine and humans. J Pathol Transl Med. 2016;50(6):426-35.
31.Gérard AC, Denef JF, Colin IM, van den Hove MF. Evidencefor processing of compact insoluble thyroglobulin globules in relation with follicular cell functional activity in the human and the mouse thyroid. Eur J Endocrinol. 2004;150(1):73-80.