Nicotine prevents disruption of the late phase LTP-related molecular cascade in adult-onset hypothyroidism.

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.