title: Chronic nicotine treatment reverses hypothyroidism-induced impairment of L-LTP induction phase: critical role of CREB.
abstract: We have previously shown that adult onset hypothyroidism impairs late-phase long-term potentiation (L-LTP) and reduces basal protein levels of cyclic-AMP response element binding protein (CREB), mutagen-activated protein kinase (MAPKp42/44), and calcium calmodulin kinase IV (CaMKIV) in area Cornu Ammonis 1 (CA1) of the hippocampus. These changes were reversed by chronic nicotine treatment. In the present study, levels of signaling molecules important for L-LTP were determined in CA1 area of the hippocampus during the induction phase. Standard multiple high-frequency stimulation (MHFS) was used to evoke L-LTP in the CA1 area of the hippocampus of hypothyroid, nicotine-treated hypothyroid, nicotine, and sham control anaesthetized adult rats. Chronic nicotine treatment reversed hypothyroidism-induced impairment of L-LTP at the induction phase. Five minutes after MHFS, Western blotting showed an increase in the levels of P-CREB, and P-MAPKp42/44 in sham-operated control, nicotine, and nicotine-treated hypothyroid animals, but not in hypothyroid animals. The protein levels of total CREB, total MAPK p42/44, BDNF, and CaMKIV were not altered in all groups 5 min after MHFS. Therefore, normalized phosphorylation of essential kinases such as P-CREB and P-MAPK p42/44 in the CA1 area of nicotine-treated hypothyroid animals plays a crucial role in nicotine-induced rescue of L-LTP induction during hypothyroidism.
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan.
authors.forename: K H
authors.initials: KH
authors.lastname: Alzoubi
authors.forename: K A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000818:Animals; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D007037:Hypothyroidism / Q000188:drug therapy* / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D009538:Nicotine