Effect of L-thyroxine administration on long-term potentiation and accompanying mitogen-activated protein kinases in rats.

The present study investigated the differences in the activation of c-Jun NH2-terminal kinases (JNK), p38 mitogen-activated protein kinases (p38MAPK ), and extracellular signal-regulated kinases 1/2 (Erk1/2) 1 hr after the induction of long-term potentiation (LTP) between rats with hyperthyroidism that was produced at two different stages of development. Hyperthyroidism was produced in rats by daily injections of L-thyroxine (T4, ip., 0.2 mg/kg) to their dams for lactation period or to the rats itself during the young adult period. LTP was induced by application of high-frequency stimulation protocol. Five-min averages of the excitatory postsynaptic potential (EPSP) slopes and population spike (PS) amplitudes at the end of recording were averaged to measure the magnitude of LTP. Total and phosphorylated levels of Erk1/2, JNK, and P38-MAPK were assessed via western blotting in these hippocampi. LTP was found to be impaired in both groups of hyperthyroidisms, but this impairment observed together with increased expression and phosphorylation of ERK1/2, and increased phosphorylation of JNK in rats treated maternally with T4 compared to those treated adultly. These results suggest that excessiveness of thyroid hormone has longstanding effects on hippocampal function and may account for failed LTP in both early and relatively late stage of development depending on various molecular pathways, such as ERK1/2 and JNK.