title: 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.
authors.affiliation: Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston, TX 77204-5515, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Alzoubi
authors.forename: A S
authors.initials: AS
authors.lastname: Bedawi
authors.forename: A M
authors.initials: AM
authors.lastname: Aleisa
authors.forename: K A
authors.initials: KA
authors.lastname: Alkadhi
mesh_terms: D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight; D019703:Calcineurin / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology / Q000528:radiation effects; D005728:Ganglia, Sympathetic / Q000473:pathology*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology*; D017774:Long-Term Potentiation / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013965:Thyroidectomy / Q000379:methods
chemical_list: D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D011494:Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C517686:Camk4 protein, rat; D019703:Calcineurin