Int. J. Devl Neuroscience 30 (2012) 83–89 Contents lists available at SciVerse ScienceDirect International Journal of Developmental Neuroscience j our na l ho me p age: www.elsevier.com/locate/ijdevneu Diphenyl diselenide diet intake improves spatial learning and memory deficits in hypothyroid female rats Glaecir Roseni Mundstock Dias a , Francielli Araújo Vieira a , Fernando Dobrachinski a , Jéssika Cristina Bridi a , Rodrigo de Souza Balk b , Félix Antunes Soares a , Cristina Wayne Nogueira a , Nilda Berenice de Vargas Barbosa a,∗ a Departamento de Química, CCNE, Programa de Pós-Graduac ¸ ão em Bioquímica Toxicológica, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil b Centro de Ciências da Saúde, Universidade Federal do Pampa (UNIPAMPA), Uruguaiana, RS, Brazil a r t i c l e i n f o Article history: Received 14 August 2011 Received in revised form 16 December 2011 Accepted 26 December 2011 Keywords: Selenium Diphenyl diselenide Hypothyroidism Methimazole Behavior a b s t r a c t Cognitive deficits have been observed in different animal models of adult-onset hypothyroidism. Thus, this study was delineated to evaluate whether diphenyl diselenide, an organoselenium compound with neuroprotective and antioxidant properties, could afford protection against the detrimental effects of hypothyroidism on behavioral parameters. Hypothyroidism condition was induced in female rats by continuous exposure to methimazole (MTZ) at 20 mg/100 ml in the drinking water, during 3 months. MTZ- induced hypothyroid rats were fed with either standard or a diet containing 5 ppm of diphenyl diselenide for 3 months. Behavioral assessments were performed monthly, in the following order: elevated plus maze, open field and Morris water maze. The levels of thyroid hormones in the animals exposed to MTZ were lower than control until the end of experimental period. The rats exposed to MTZ had a significant weight loss from the first month, which was not modified by diphenyl diselenide supplementation. In elevated plus maze test, MTZ exposure caused a reduction on the number of entries of animals in closed arms, which was avoided by diphenyl diselenide supplementation. In Morris water maze, the parameters latency to reach the platform and distance performed to find the escape platform in the test session were significantly greater in MTZ group when compared to control. These cognitive deficits observed in MTZ-induced hypothyroid rats were restored by dietary diphenyl diselenide. The group fed with diphenyl diselenide alone exhibited a better spatial learning and memory capability in some parameters of Morris water maze when compared to the control group. In summary, our data provide evidence of the effectiveness of dietary diphenyl diselenide in improving the performance of control and hypothyroid rats in the water maze test. © 2012 ISDN. Published by Elsevier Ltd. All rights reserved. 1. Introduction Hypothyroidism is one of the most common thyroid disorders in the general population, especially prevalent in women (Morganti et al., 2005). Clinical observations have shown that this thyroid dis- ease is closely related to psychiatric and cognitive disorders, such as impaired memory, anxiety and depression (Demet et al., 2002; Van Boxtel et al., 2004; Guimarães et al., 2009). In fact, the thyroid hor- mones are essential for maturation and normal brain functions in vertebrates and their deficiency, especially during a critical period ∗ Corresponding author at: Departamento de Química, Prédio 19, sala 3239, Uni- versidade Federal de Santa Maria 97105.900, Santa Maria, RS, Brazil. Tel.: +55 55 3220 8140; fax: +55 55 3220 8240. E-mail address: nvbarbosa@yahoo.com.br (N.B.d.V. Barbosa). of development, affects cognitive functions and learning (Darbra et al., 1995, 2003; Vara et al., 2002; Sala-Roca et al., 2008). It has been postulated that the thyroid gland requires high concentrations of selenium for selenoproteins expression, which are important in maintaining the physiological levels of active hormones T3 (triiodothyronine) and T4 (thyroxine) (Köhrle, 1999; Köhrle and Gärtner, 2009); and that selenium deficiency is linked with a decrease in the levels of these hormones (Arthur et al., 1992, 1993). Really, this trace element is con- sidered essential to the biosynthesis, activation and metabolism of the thyroid hormones (Köhrle, 1999; Köhrle and Gärtner, 2009). The importance of selenium to the thyroid hormone biosyn- thesis came from myxedematous cretinism cases, predominantly observed in Central Africa, which can be caused by combined iodine and selenium deficiency with exposure to nutritional goitrogens (Vanderpas et al., 1990). In this context, experimental evidence 0736-5748/$36.00 © 2012 ISDN. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijdevneu.2011.12.011