PMID- 20021662 OWN - NLM STAT- MEDLINE DCOM- 20100212 LR - 20211020 IS - 1471-2202 (Electronic) IS - 1471-2202 (Linking) VI - 10 DP - 2009 Dec 18 TI - Developmental iodine deficiency resulting in hypothyroidism reduces hippocampal ERK1/2 and CREB in lactational and adolescent rats. PG - 149 LID - 10.1186/1471-2202-10-149 [doi] AB - 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. FAU - Dong, Jing AU - Dong J AD - Department of Occupational and Environmental Health, School of Public Health, China Medical University, Shenyang, PR China. dj814@163.com FAU - Liu, Wanyang AU - Liu W FAU - Wang, Yi AU - Wang Y FAU - Hou, Yi AU - Hou Y FAU - Xi, Qi AU - Xi Q FAU - Chen, Jie AU - Chen J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20091218 PL - England TA - BMC Neurosci JT - BMC neuroscience JID - 100966986 RN - 9679TC07X4 (Iodine) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.3.1.48 (CREB-Binding Protein) RN - EC 2.3.1.48 (Crebbp protein, rat) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - CREB-Binding Protein/*metabolism MH - Cyclic AMP/metabolism MH - Disease Models, Animal MH - Down-Regulation MH - Hippocampus/*growth & development/metabolism/pathology MH - Hypothyroidism/pathology/*physiopathology MH - Iodine/*deficiency MH - Lactation/metabolism MH - Learning Disabilities/*metabolism MH - Memory Disorders/*metabolism MH - Mitogen-Activated Protein Kinase 3/*metabolism MH - Neurons/metabolism/pathology MH - Random Allocation MH - Rats MH - Rats, Wistar PMC - PMC2804698 EDAT- 2009/12/22 06:00 MHDA- 2010/02/13 06:00 PMCR- 2009/12/18 CRDT- 2009/12/22 06:00 PHST- 2009/09/29 00:00 [received] PHST- 2009/12/18 00:00 [accepted] PHST- 2009/12/22 06:00 [entrez] PHST- 2009/12/22 06:00 [pubmed] PHST- 2010/02/13 06:00 [medline] PHST- 2009/12/18 00:00 [pmc-release] AID - 1471-2202-10-149 [pii] AID - 10.1186/1471-2202-10-149 [doi] PST - epublish SO - BMC Neurosci. 2009 Dec 18;10:149. doi: 10.1186/1471-2202-10-149.