Hypothyroidism following developmental iodine deficiency reduces hippocampal neurogranin, CaMK II and calmodulin and elevates calcineurin in lactational rats

Abstract

Developmental iodine deficiency (ID) leads to inadequate thyroid hormone that impairs learning and memory with an unclear mechanism. Here, we show that hippocampal neurogranin, calcium/calmodulin dependent protein kinase II (CaMKII), calmodulin (CaM) and calcineurin (CaN) are implicated in the brain impairment in lactational rat hippocampus following developmental ID and hypothyroidism. 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) 21. Then, the neurogranin, CaMKII, CaM and CaN in the hippocampus were detected with immunohistochemistry and western blotting on PN14 and PN21. The iodine-deficient and hypothyroid pups showed significantly lower level of neurogranin, CaMKII and CaM and significantly increased CaN in hippocampal CA1 and CA3 regions than the controls on PN14 and PN21 (P<0.05, respectively). Data indicate that, in lactational rats, hippocampal neurogranin, CaMKII, CaM and CaN are involved in the brain impairment by developmental ID and hypothyroidism.