title: Nicotine prevents disruption of the late phase LTP-related molecular cascade in adult-onset hypothyroidism.
abstract: We have shown previously that chronic nicotine treatment reverses adult-onset hypothyroidism-induced impairment of late-phase long-term potentiation (L-LTP) 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. Immunoblots analysis showed that chronic nicotine treatment of hypothyroid rats prevented the reduction in the basal protein levels of adenylyl cyclase I (ACI), mitogen-activated protein kinases [MAPKp44/42 (ERK1/2)], calcium-calmodulin-dependent protein kinase IV (CaMKIV), and cyclic-AMP response element binding protein [CREB; phosphorylated (P-) and total]. A significant increase in the levels of P-CREB, P-MAPKp44, P-MAPKp42 and brain derived neurotrophic factor (BDNF) was seen 4 h after multiple train high frequency stimulation (MHFS) in nicotine-treated hypothyroid and control animals, but not in hypothyroid animals. The levels of total CREB, total MAPKp44, total MAPKp42, and CaMKIV were elevated in all groups 4 h after MHFS. These findings suggest that prevention of the reduced basal level of CaMKIV, MAPKp44/42, and CREB by nicotine along with the regained ability of MHFS to induce MAPKp44/42 and CREB phosphorylation in nicotine treated hypothyroid animals may be responsible for the reversal of L-LTP impairment by chronic nicotine treatment in this disease model.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, Texas 77204-5515, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Alzoubi
authors.forename: A M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: K A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D050882:CREB-Binding Protein / Q000378:metabolism; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006624:Hippocampus / Q000187:drug effects / Q000528:radiation effects; D007037:Hypothyroidism / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008954:Models, Biological; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018722:Nicotinic Agonists; D009538:Nicotine; D050882:CREB-Binding Protein; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517686:Camk4 protein, rat; D020929:Mitogen-Activated Protein Kinase Kinases; D000262:Adenylyl Cyclases