Koromilas Christos, Tsakiris Stylianos, Kalafatakis Konstantinos, Zarros Apostolos, Stolakis Vasileios, Kimpizi Despoina, Bimpis Alexios, Tsagianni Anastasia, Liapi Charis
Laboratory of Pharmacology, Medical School, National and Kapodistrian University of Athens, Athens, Greece.
Metab Brain Dis. 2015 Feb;30(1):241-6. doi: 10.1007/s11011-014-9581-9. Epub 2014 Jun 29.
Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent approaches towards the experimental simulation of congenital and early-age-occurring hypothyroidism.
神经发育过程中甲状腺激素不足可导致发育中的中枢神经系统（CNS）出现显著的结构和功能变化，并与严重认知障碍和神经精神症状的形成有关。本研究的目的是通过多水平实验方法，以脑区特异性方式研究妊娠和/或哺乳期母体暴露于丙硫氧嘧啶（PTU）诱导的甲状腺功能减退对21日龄Wistar大鼠后代关键脑酶活性的影响。这种实验方法是作者最近基于对新生和21日龄大鼠后代全脑匀浆进行的神经化学分析而开发和表征的；作为这一工作的延续，本研究聚焦于对认知发育具有重要意义的两个中枢神经系统区域：额叶皮质和海马体。妊娠和/或哺乳期母体通过饮用含PTU的水暴露后，乙酰胆碱酯酶以及两种重要的三磷酸腺苷酶（Na(+)，K(+)-ATP酶和Mg(2+)-ATP酶）的活性发生了变化，这些变化似乎以中枢神经系统区域特异性方式发生，并且取决于所遵循的PTU暴露时间框架。当对这些发现进行分析并与现有文献进行比较时，它们：（i）突出了所研究的中枢神经系统区域中上述酶参数变化所涉及的变异性（这归因于不同的神经解剖组成以及后者的甲状腺激素依赖性神经发育生长/分化模式），（ii）揭示了关于临床甲状腺功能减退可能影响最佳神经发育以及最终认知功能的方式中可能涉及的神经化学机制的重要信息，以及（iii）强调了在先天性和早期发生的甲状腺功能减退的实验模拟中采用更一致方法的必要性。
