In vitro Effect of Thyroxine on Cholinergic Neurotransmission in Rat Sympathetic Superior Cervical Ganglion

Abstract

This study aimed at examining the effect of thyroid hormones on cholinergic transmission in isolated rat superior cervical ganglia (SCG). In SCG explants incubated with ³H-choline, thyroxine (T4) and 3,3’,5-triiodothyronine (T3) added to the medium before a second depolarization stimulus of 60 mM K⁺ resulted in a dose-dependent increase of S2/S1 ratio for ³H release. The concentration of hormone that produced 50% of maximal increase in K⁺-induced radioactivity release was 8 × 10^–9 M for T4 and 1.6 × 10^–8M for T3 while 3,3’,5,5’-tetraiodothyroacetic acid was almost ineffective. Preincubation of SCG with 10^–7M iopanoic acid for 30 min before S2, although not affecting by itself S2/S1 ratio, effectively prevented the increase given by T4 or T3. ³H-acetylcholine release by SCG was augmented in a high K⁺ and the effect was amplified by T4 to a similar extent as that for total ³H release. When added to the incubation medium together with 60 mM K⁺ for 30 min, T4 (10^–7M) increased significantly the activity of choline acetyltransferase (ChAT). T4 did not affect ChAT activity in SCG exposed to 4.7 mM K⁺, nor in SCG homogenates. ³H-choline uptake measured immediately after exposure of SCG to 60 mM K⁺ decreased by 25%, whereas it increased by 71% after a subsequent 30-min incubation with 4.7 mM K⁺. Addition of 10^–7M T4 prevented the changes in choline uptake observed in a high K⁺ medium. These results indicate that T4 increases SCG cholinergic transmission.

Critical Period Regulation by Thyroid Hormones: Potential Mechanisms and Sex-Specific Aspects

“…It is thus possible that early life TH levels influence cholinergic transmission to regulate plasticity. Additional evidence supporting this view comes from in vitro studies where both release and synthesis of acetylcholine is enhanced by T4 application (Landa et al, 1991). Additionally, cholinergic deficits in the Snell Dwarf Mouse are corrected by T4 injections (Fuhrmann et al, 1986), suggesting that TH-mediated modulation of cholinergic transmission occurs in vivo .…”

Thyroid Hormone Effects on Sensory Perception, Mental Speed, Neuronal Excitability and Ion Channel Regulation

“…(156)). Although smaller and more localized effects are reported in adults, several lines of evidence suggest that acetylcholine -release may be enhanced by thyroid hormone and decreased in hypothyroidism in the adult nervous system as well (157,158). A decrease of cholinergic activity could perhaps also explain the occurrence of slow EEG waves (159) as well as the cognitive impairments frequently seen in hypothyroid subjects.…”

“…In addition T3 could act as a cotransmitter to modulate noradrenergic action (169) or as a modulator of endogenous benzodiazepine action (170). While it is believed that thyroid hormone exerts its effects predominantly via nuclear receptors possible direct effects on membrane receptors further complicate the picture (157,171,172). In addition to a membrane action via V 3intergins, high doses of 20 µM T3 or T4 have been shown to directly act on GABA receptors to down-regulate GABAergic postsynaptic currents in cultured hippocampal neurons (173,174), which could explain acute increases in neuronal excitability induced by iontophoretecally injected T4 and T3 (171).…”

Involvement of L-Triiodothyronine in Acetylcholine Metabolism in Adult Rat Cerebrocortical Synaptosomes

“…TH-treatment also increased muscarinic cholinoceptor levels, choline acetyltransferase (ChAT) activity in 16-day fetal rat whole brain reaggregate cell culture [5], and almost restored depressed ChAT activity in polychlorinated biphenyl-induced hypothyroidism in the hippocampus and basal forebrain of 15-day old neonatal rats [6]. L-thyroxin (T 4 ) also enhanced the ChAT activity and [ 3 H]-acetylcholine (Ach) release in isolated rat superior cervical ganglia (SCG) after high K + -induction [7]. Hyperthyroidism showed a 30 % decrease and hypothyroidism showed 40 % increase in the muscarinic receptor levels in cerebellum of neonatal rats [8].…”