Molecular studies on the protective effect of nicotine in adult-onset hypothyroidism-induced impairment of long-term potentiation.

We have recently shown that chronic nicotine treatment reverses hypothyroidism-induced learning and memory impairment. Chronic nicotine treatment also reverses the hypothyroidism-induced impairment of long-term potentiation (LTP). Analysis of LTP associated key signaling molecules revealed that chronic nicotine treatment prevented the hypothyroidism-induced reduction of the basal phosphotransferase activity of CaMKII and protein levels of P-CaMKII. In addition, the failure of high frequency stimulation to increase the levels of P-CaMKII in hypothyroid rats was reversed by nicotine treatment, suggesting that the neuroprotective effect of nicotine during hypothyroidism involved activation of CaMKII. Furthermore, chronic nicotine treatment reverses the hypothyroidism-induced elevated phosphatase activity and protein levels of calcineurin, a phosphatase that regulates CaMKII activation. We conclude that the neuroprotective effects of nicotine in adult-onset hypothyroidism may result from restoration of CaMKII and calcineurin activity. 2006 Wiley-Liss, Inc.