title: Developmental hypothyroxinemia caused by mild iodine deficiency leads to HFS-induced LTD in rat hippocampal CA1 region: involvement of AMPA receptor.
abstract: Hypothyroidism induced by severe iodine deficiency (ID) during developmental period seriously damages the central nervous system function. In addition to developmental hypothyroidism induced by severe ID, developmental hypothyroxinemia induced by mild ID is potentially damaging for neurodevelopment and learning and memory in children. Wistar rats were treated with iodine-deficient diet or methimazole (MMZ) during pregnancy and lactation to induce developmental hypothyroxinemia or hypothyroidism in the present study. Pups were weaned on postnatal day (PN) 21 and used for electrophysiological recordings on PN80. It is generally accepted that long-term depression (LTD) is induced at low-frequency stimulation (LFS) in hippocampal CA1 region. Surprisingly, we observed developmental hypothyroxinemia as well as developmental hypothyroidism led to high-frequency stimulation (HFS)-induced LTD in hippocampal CA1 region. The abnormal HFS-induced LTD suggests not only developmental hypothyroidism but also developmental hypothyroxinemia impairs learning and memory. To explore the mechanisms responsible for the HFS-induced LTD, the phosphorylation status of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) was investigated. The results showed that developmental hypothyroxinemia as well as developmental hypothyroidism decreased the phosphorylation of AMPAR subunit glutamate receptor 1 (GluR1) at serine 831 and serine 845 in hippocampal CA1 region. Neither developmental hypothyroxinemia nor developmental hypothyroidism altered the phosphorylation of AMPAR subunit glutamate receptor 2 (GluR2) at serine 880. Increased levels of protein phosphatase-1 (PP1) were also observed in hippocampal CA1 regions of pups subjected to developmental hypothyroxinemia or hypothyroidism. Taken together, our results suggest that the increased levels of PP1 caused by developmental hypothyroxinemia or hypothyroidism may account for the dephosphorylation of GluR1 at serine 831 and serine 845, which may contribute to HFS-induced LTD in hippocampal CA1 region.
authors: Department of Occupational and Environmental Health, School of Public Health, China Medical University, 92 North 2nd Road, Shenyang, 110001, People's Republic of China.
authors: Yi
authors: Y
authors: Wang
authors: Wei
authors: W
authors: Wei
authors: Binbin
authors: B
authors: Song
authors: Yuan
authors: Y
authors: Wang
authors: Jing
authors: J
authors: Dong
authors: Hui
authors: H
authors: Min
authors: Jie
authors: J
authors: Chen
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D005260:Female; D007037:Hypothyroidism / Q000378:metabolism*; D007455:Iodine / Q000172:deficiency*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D054645:Protein Phosphatase 1 / Q000378:metabolism; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D007455:Iodine; D054645:Protein Phosphatase 1