Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats.
BACKGROUND
Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal extracellular signal-regulated kinase (ERK1/2) and cAMP response element-binding protein (CREB) are implicated in the impaired learning and memory in lactational and adolescent rat hippocampus following developmental ID and hypothyroidism.


METHODS
Three developmental rat models were created by administrating dam rats with either iodine-deficient diet or propylthiouracil (PTU, 5 ppm or 15 ppm)-added drinking water from gestational day (GD) 6 till postnatal day (PN) 28. Then, the total and phorsporylated ERK1/2 and total and phorsporylated CREB in the hippocampus were detected with western blot on PN14, PN21, PN28 and PN42.


RESULTS
The iodine-deficient and hypothyroid pups showed lower serum FT3 and FT4 levels, smaller body size, and delayed eyes opening. The mean number of surviving cells in the hippocampus of the iodine-deficient and 15 ppm PTU-treated rats was significantly reduced compared to controls (P < 0.05). Iodine-deficient and 15 ppm PTU-treatment groups demonstrated significantly lower level of total and phosphorylated ERK1/2 and CREB than the controls on PN14, PN21 and PN28 (P < 0.05, respectively). The reduction of ERK1/2 and CREB was not reversible with the restoration of serum thyroid hormone concentrations on PN42.


CONCLUSIONS
Developmental ID and hypothyroidism down-regulate hippocampal ERK1/2 and CREB in lactational and adolescent rats.
Dong
Jing
J
Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, PR China. dj814@163.com
Liu
Wanyang
W
Wang
Yi
Y
Hou
Yi
Y
Xi
Qi
Q
Chen
Jie
J
D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism / Q000473:pathology; D007037:Hypothyroidism / Q000473:pathology / Q000503:physiopathology*; D007455:Iodine / Q000172:deficiency*; D007774:Lactation / Q000378:metabolism; D007859:Learning Disabilities / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D007455:Iodine; D000242:Cyclic AMP; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D048052:Mitogen-Activated Protein Kinase 3