کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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3055921 | 1186544 | 2011 | 8 صفحه PDF | دانلود رایگان |
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.
Research Highlights
► Hypothyroxinemia alters neocortical thyroid hormone responsiveness and action.
► Evidence of insufficient homeostatic response to low T4 during development
► Hypothyroxinemia impairs nuclear/mitochondrial gene expression and cell survival.
Journal: Experimental Neurology - Volume 228, Issue 1, March 2011, Pages 91–98