Thyroid hormones reduce nicotinic receptor mediated currents in SH-SY5Y neuroblastoma cells
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Thyroid hormones reduce nicotinic receptor mediated currents in SH‑SY5Y neuroblastoma cells Giulia Puia1 · Federica Ravazzini1 Received: 7 November 2019 / Revised: 24 September 2020 / Accepted: 5 October 2020 © Maj Institute of Pharmacology Polish Academy of Sciences 2020
Abstract Background Thyroid hormones (THs) are crucial for maturation and functioning of mammalian CNS. THs “classical” signaling involves nuclear receptors binding but also their non genomic actions, as rapid modulators of cell activity, are widely recognized. Since THs imbalance affects cognition and the cholinergic system is deeply involved in learning and memory processes we have studied THs effects at the level of the nicotinic acetylcholine receptors (nAchR). Methods We used the patch-clamp technique to analyze T3 and T4 modulation of nicotine (NIC)-mediated current in SHSY5Y neuroblastoma cells. Results Both hormones decreased NIC-evoked current in a dose dependent fashion. The antagonism was reversible, not competitive and not blocked by Tetrac, an integrin αVβ3 receptor antagonist. A similar effect was detected with the endogenous agonist Acetylcholine. THs potencies were higher at 100 μM NIC ( IC50 = 4.6 ± 2 μM for T3 and 4.8 ± 2 μM for T4) compared to those measured at 10 μM NIC (IC50 = 10 ± 4 μM for T3 and 8 ± 4 μM for T4). Furthermore, the efficacy of THs reached almost 90% at 100 μM NIC while was about 30 % at 10 μM NIC. THs inhibited nAchR-mediated currents by enhancing receptor desensitization and this effect was more pronounced at high agonist concentrations. Conclusions Our results make light on a new non genomic activity of THs at the level of nAchR. This mechanism of action of THs can provide a new explanation for the cognitive deficits associated with tyroid dysfunction. Keywords Thyroid hormones · Nicotinic receptor · Patch-clamp technique · SH-SY5Y neuroblastoma cells Abbreviations CNS Central nervous system T3 Triiodothyronine T4 Thyroxine Tetrac Tetraiodothyroacetic acid
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43440-020-00170-7) contains supplementary material, which is available to authorized users. * Giulia Puia [email protected] 1
Department of Life Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41100 Modena, Italy
Introduction Thyroid hormones (THs) play a fundamental role in the development and maturation of CNS; moreover, they are important modulators of brain functions also during adulthood. There are two major types of THs in the CNS: l‐triiodothyronine (T3) and l‐thyroxine (T4). T4 is the main hormone secreted by the thyroid gland, while T3 is also produced locally within the brain tissue by 5′‐deiodination of T4. The “classical” mechanism of action of THs is genomic: by binding to nuclear receptors (TRα and TRβ) they regulate gene expression. THs genomic effects are indeed considered staminal for brain development but less important for adult brain function [1]. In the last decades many studies pro
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