Hypothyroidism impairs long‐term potentiation in sympathetic ganglia: Electrophysiologic and molecular studies

Abstract

Electrophysiologic and molecular techniques were used to study the effect of adult-onset hypothyroidism on synaptic plasticity in the superior cervical sympathetic ganglion. Ganglia excised from adult thyroidectomized and sham-operated rats were subjected to a brief high-frequency stimulation of the preganglionic nerve to express long-term potentiation (gLTP). Western blotting was carried out to determine the protein levels of key signaling molecules that may be involved in the expression of gLTP. Input/output relationship in ganglia from hypothyroid rats indicated a normal basal synaptic transmission, whereas activity-dependent types of synaptic plasticity, posttetanic potentiation (PTP) and gLTP, were impaired. Immunoblot analysis showed that both calcium/calmodulin kinase II (CaMKII) and phosphorylated CaMKII (P-CaMKII) levels were reduced markedly in hypothyroid rat ganglia compared to those from euthyroid controls. Additionally, protein levels of nitric oxide synthase-1, heme oxygenase-2, calmodulin, protein kinase C (PKC), and calcineurin were also reduced in hypothyroid rat ganglia. The results indicate that abnormally low basal levels of signaling molecules may be responsible for hypothyroidism-induced impairment of gLTP in superior cervical ganglia. In addition, the results indicate that synaptic plasticity in sympathetic ganglia may involve a molecular sequence of events similar to that proposed for LTP in the hippocampus.