Int. J. Devl Neuroscience 35 (2014) 1–6 Contents lists available at ScienceDirect International Journal of Developmental Neuroscience j ourna l ho me page: www.elsevier.com/locate/ijdevneu Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities Christos Koromilas a,b , Charis Liapi a , Apostolos Zarros b,c , Vasileios Stolakis a,b , Anastasia Tsagianni b , Nikolina Skandali b , Hussam Al-Humadi d , Stylianos Tsakiris b,∗ a Laboratory of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece b Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece c Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK d Department of Pharmacology, College of Pharmacy, University of Babylon, Babylon, Iraq a r t i c l e i n f o Article history: Received 13 October 2013 Received in revised form 15 February 2014 Accepted 4 March 2014 Keywords: Hypothyroidism Propylthiouracil Gestation Lactation Acetylcholinesterase Na + ,K + -ATPase Mg 2+ -ATPase Rat Brain a b s t r a c t Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological prob- lems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na + ,K + -ATPase and Mg 2+ -ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned cru- cial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelop- mental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. © 2014 ISDN. Published by Elsevier Ltd. All rights reserved. 1. Introduction Thyroid hormones (THs), thyroxine (T4) and 3,5,3’- triiodothyronine (T3), are known to exert a broad spectrum of effects on the central nervous system (CNS), during both development and adulthood (Bernal, 2007; Brabant et al., 2011; Calzà et al., 1997; Jahagirdar and McNay, 2012). Within the developing CNS, THs modulate a significant number of factors involved in neuronal migration, growth, differentiation and signalling (Williams, 2008), and are reported to play an important ∗ Corresponding author at: Laboratory of Physiology, Medical School, National and Kapodistrian University of Athens, PO Box 65257, GR-15401 Athens, Greece. Tel.: +30 210 7462662; fax: +30 210 7462571. E-mail addresses: stsakir@med.uoa.gr, stsakir@gmail.com (S. Tsakiris). role in the maturation of the synaptic plasma membrane during neurodevelopment (Lindholm, 1984). Hypothyroidism during neurodevelopment may cause extended structural and functional alterations to certain cru- cial CNS regions (Koromilas et al., 2010) that can even lead to irreversible mental retardation and neurological deficits (Abduljabbar and Afifi, 2012; Morreale de Escobar, 2003). Experi- mental simulation of hypothyroidism during neurodevelopment can be achieved through multiple in vivo models (Argumedo et al., 2012); among these, the maternal administration of propylth- iouracil (PTU) in the drinking water during rodent gestation and/or lactation has been the most popular and can be considered as amongst the easiest to perform. During the last decade, we have provided a number of reports on the effects of PTU-induced adult-onset hypothyroidism on crucial neurochemical parameters such as the activity of acetyl- cholinesterase (AChE) and of two major adenosinetriphosphatases http://dx.doi.org/10.1016/j.ijdevneu.2014.03.002 0736-5748/© 2014 ISDN. Published by Elsevier Ltd. All rights reserved.