NDLI: Developmental Hypothyroxinemia and Hypothyroidism Reduce Proliferation of Cerebellar Granule Neuron Precursors in Rat Offspring by Downregulation of the Sonic Hedgehog Signaling Pathway

Content Provider	Springer Nature Link
Author	Wang, Yuan Wang, Yi Dong, Jing Wei, Wei Song, Binbin Min, Hui Yu, Ye Lei, Xibing Zhao, Ming Teng, Weiping Chen, Jie
Copyright Year	2013
Abstract	Iodine deficiency (ID)-induced hypothyroxinemia and hypothyroidism during development result in dysfunction of the central nervous system, affecting psychomotor and motor function, although the underlying mechanisms causing these alterations are still unclear. Therefore, our aim is to study the effects of developmental hypothyroxinemia, caused by mild ID, and developmental hypothyroidism, caused by severe ID or methimazole (MMZ), on the proliferation of cerebellar granule neuron precursors (CGNPs), an excellent experimental model of cerebellar development and function. The sonic hedgehog (Shh) signaling pathway is essential for CGNP proliferation, and as such, its activation is also investigated here. A maternal hypothyroxinemia model was established in Wistar rats by administrating a mild ID diet, and two maternal hypothyroidism models were developed either by administrating a severe ID diet or MMZ water. Our results showed that hypothyroxinemia and hypothyroidism reduced proliferation of CGNPs on postnatal day (PN) 7, PN14, and PN21. Accordingly, the mean intensity of proliferating cell nuclear antigen and Ki67 nuclear antigen immunofluorescence was reduced in the mild ID, severe ID, and MMZ groups. Moreover, maternal hypothyroxinemia and hypothyroidism reduced expression of the Shh signaling pathway on PN7, PN14, and PN21. Our study supports the hypothesis that developmental hypothyroxinemia induced by mild ID, and hypothyroidism induced by severe ID or MMZ, reduce the proliferation of CGNPs, which may be ascribed to the downregulation of the Shh signaling pathway.
Starting Page	1143
Ending Page	1152
Page Count	10
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	49
Issue Number	3
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2013-11-22
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Iodine deficiency Hypothyroxinemia Hypothyroidism Cerebellar granule neuron precursors Proliferation Shh signaling pathway Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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