title: Different Degrees of Iodine Deficiency Inhibit Differentiation of Cerebellar Granular Cells in Rat Offspring, via BMP-Smad1/5/8 Signaling.
abstract: Iodine deficiency (ID) during development results in dysfunction of the central nervous system (CNS) and affects psychomotor and motor function. It is worth noting that maternal mild and marginal ID tends to be the most common reason of preventable neurodevelopmental impairment, via a mechanism that has not been elucidated. Therefore, our aim was to study the effects of developmental mild and marginal ID on the differentiation of cerebellar granule cells (GCs) and investigate the activation of BMP-Smad1/5/8 signaling, which is crucial for the development and differentiation of cerebellum. Three developmental rat models were created by feeding dam rats with a diet deficient in iodine and deionized water supplemented with potassium iodide. Our results showed that different degrees of ID inhibited and delayed the differentiation of cerebellar GCs on postnatal day (PN) 7, PN14, and PN21. Moreover, mild and severe ID reduced the expression of BMP2 and p-Smad1/5/8, and increased the levels of Id2 on PN7, PN14, and PN21. However, marginal ID rarely altered expression of these proteins in the offspring. Our study supports the hypothesis that mild and severe ID during development inhibits the differentiation of cerebellar GCs, which may be ascribed to the down-regulation of BMP-Smad1/5/8 signaling and the overexpression of Id2. Furthermore, it was speculated that maternal marginal ID rarely affected the differentiation of cerebellar GCs in the offspring.
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Jing
authors: J
authors: Dong
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Xibing
authors: X
authors: Lei
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Yi
authors: Y
authors: Wang
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Yuan
authors: Y
authors: Wang
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Heling
authors: H
authors: Song
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Min
authors: M
authors: Li
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Hui
authors: H
authors: Min
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China.
authors: Ye
authors: Y
authors: Yu
authors: Department of Physiology, University of Tennessee Health Science Center, Memphis, TN, 38163, USA.
authors: Qi
authors: Q
authors: Xi
authors: Liaoning Provincial Key Laboratory of Endocrine Diseases, First Hospital of China Medical University, Shenyang, 110001, Peoples' Republic of China. twp@vip.163.com.
authors: Weiping
authors: W
authors: Teng
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, No. 77 Puhe Road, Shenyang, 110122, Peoples' Republic of China. chenjie@mail.cmu.edu.cn.
authors: Jie
authors: J
authors: Chen
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology* / Q000378:metabolism*; D005260:Female; D007455:Iodine / Q000172:deficiency*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D051896:Smad Proteins, Receptor-Regulated / Q000096:biosynthesis*; D051898:Smad1 Protein / Q000096:biosynthesis; D051902:Smad5 Protein / Q000096:biosynthesis; D051904:Smad8 Protein / Q000096:biosynthesis
chemical_list: C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D051896:Smad Proteins, Receptor-Regulated; D051898:Smad1 Protein; C497400:Smad1 protein, rat; D051902:Smad5 Protein; C497799:Smad5 protein, rat; D051904:Smad8 Protein; C109462:Smad9 protein, rat; D007455:Iodine
keywords: BMP-Smad1/5/8 signaling; Cerebellum; Differentiation; Granular cells; Id2; Marginal iodine deficiency; Mild iodine deficiency