Department of Endocrinology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, India.
Exp Neurol. 2011 Mar;228(1):91-8. doi: 10.1016/j.expneurol.2010.12.012. Epub 2010 Dec 24.
Neurological deficits due to maternal and neonatal hypothyroxinemia under mild-moderate iodine deficiency are a major preventable health problem worldwide. The present study assesses the impact of hypothyroxinemia on postnatal neocortical development and also compares it to the known effects of severe hypothyroidism. Our results strongly suggest that even within elevated circulating triiodothyronine (T3) levels, hypothyroxinemia significantly impairs thyroid hormone responsiveness in developing rat neocortex. The significant compensatory alteration in deiodinase levels with unaltered monocarboxylate transporter 8 (MCT8) and thyroid hormone receptors (TRs), although found to be similar in hypothyroxinemic and hypothyroid condition, is more pronounced under later condition. The resultant downregulation of nuclear myelin binding protein (MBP) and mitochondrial transcripts Cytochrome oxidase III (Cox III) as well as significantly enhanced mitochondrial localization of Bax and reduced Bcl-2 and Bcl-xL accompanied by enhanced release of Cytochrome c and Smac with activation of caspase-3 indicates pronounced apoptosis leading to compromised cellular survival. The similarities of this responsiveness albeit with difference in degree under hypothyroidism and hypothyroxinemic state with adequate availability of T3 are suggestive of an independent role of thyroxine in neocortex development. Taken together, this study brings forth the neurophysiological aspects of hypothyroxinemia and underscores the importance of adequate iodine nutrition along with mandatory thyroxin monitoring during pregnancy and after birth.
由于母体和新生儿甲状腺功能减退症导致的轻度至中度碘缺乏引起的神经发育缺陷是全球范围内一个主要的可预防健康问题。本研究评估了甲状腺功能减退症对产后新皮质发育的影响，并将其与严重甲状腺功能减退症的已知影响进行了比较。我们的研究结果强烈表明，即使在循环三碘甲状腺原氨酸（T3）水平升高的情况下，甲状腺功能减退症也会显著损害发育中大鼠新皮质的甲状腺激素反应性。尽管在甲状腺功能减退症和甲状腺功能减退症条件下发现脱碘酶水平的代偿性改变相似，但在后期条件下更为明显。核髓鞘结合蛋白（MBP）和线粒体转录物细胞色素氧化酶 III（Cox III）的核下调以及 Bax 的线粒体定位增加和 Bcl-2 和 Bcl-xL 的减少伴随着细胞色素 c 和 Smac 的释放增加以及 caspase-3 的激活表明明显的细胞凋亡导致细胞存活受损。这种反应的相似性，尽管在甲状腺功能减退症和甲状腺功能减退症状态下程度不同，但在 T3 充足的情况下，提示甲状腺素在新皮质发育中具有独立作用。综上所述，这项研究提出了甲状腺功能减退症的神经生理学方面，并强调了在怀孕期间和出生后必须进行充足的碘营养和甲状腺素监测。
