A critical role of CREB in the impairment of late-phase LTP by adult onset hypothyroidism.
We have shown previously that adult onset hypothyroidism impairs late-phase long-term potentiation (L-LTP) and reduces the protein levels of mitogen-activated protein kinases (MAPKp44/42 (ERK1/2)) in area CA1 of the hippocampus. In the present study, basal and stimulated levels of signaling molecules essential for the expression of L-LTP were determined in area CA1 of the hippocampus. L-LTP was evoked by multiple train high-frequency stimulation (MHFS) in area CA1 of the hippocampus of thyroidectomized and sham control anesthetized adult rats. Immunoblot analysis showed reduction in the basal protein levels of adenylyl cyclase I (ACI), calcium calmodulin-dependent protein kinase IV (CaMKIV), and cyclic-AMP response element-binding protein (CREB; phosphorylated (P-) and total) in hypothyroid rats. A significant increase in the levels of P-CREB, P-MAPKp44 and P-MAPKp42 was seen 4 h after MHFS in sham-operated control animals, but not in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42 and CaMKIV were elevated in both groups 4 h after MHFS. Our results suggest that in adult hypothyroid rats, the reduced basal level of CaMKIV, MAPKp44/42 and CREB along with the failure of MHFS to induce MAPKp44/42 and CREB phosphorylation may be responsible for L-LTP impairment in the CA1 area during hypothyroidism.
Alzoubi
K H
KH
Department Pharmacological and Pharmaceutical Sciences, University of Houston, Houston, TX 77204-5515, USA. khalzoubi@just.edu.jo
Alkadhi
K A
KA
D000262:Adenylyl Cyclases; D000818:Animals; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D004558:Electric Stimulation; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D007037:Hypothyroidism / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D008569:Memory Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy
D017362:Cyclic AMP Response Element-Binding Protein; D011494:Protein Kinases; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517686:Camk4 protein, rat; D048052:Mitogen-Activated Protein Kinase 3; D000262:Adenylyl Cyclases