Thyroid hormones (THs) play a crucial role for the correct functioning of the mammalian central nervous system. Their genomic actions are well known and recently the attention has been focused on their novel non-genomic effects as modulators of several neurotransmitter systems (Losi et al. 2008, Puia et. al 2011). Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the brain and play important roles in regulating neuronal activity in several brain areas. By using the patch clamp technique in the whole cell configuration, we tested the effect of THs on nAChRs expressed in SHSY5Y neuroblastoma cells, in primary cultures of cortical neurons and in 293 HEK cell lines. In SHSY5Y, THs showed a dose-dependent reduction of nicotine (NIC) (10μM) current ( IC50 T3 10+/- 2 μM; IC50 T4 7+/- 2.5 μM). Their effect was not competitive and more pronounced at high agonist concentrations. Similar results were obtained using Acetylcholine (Ach) as agonist. THs reduced NIC current in cortical neurons even though their modulatory effects were variable and less marked. To test possible subunit specificity for T3 and T4 modulation, we analyze their effect in HEK293 cells expressing α4β2 nAChRs. T3 (1μM) reduced Ach (1μM)-evoked current of 32 +/- 9 % and T4 of 26 +/- 6 %. It's well known that several cognitive impairments have been resulted from THs deficiency and since “nicotinic circuits” are deeply implicated in learning and memory processes, is possible that also the reported non genomic effect of these hormones could regulate brain function.
NON GENOMIC EFFECTS OF THYROID HORMONES ON NICOTINIC NEUROTRANSMISSION / Puja, Giulia. - (2013). (Intervento presentato al convegno SINS tenutosi a Roma nel settembre 2013).
NON GENOMIC EFFECTS OF THYROID HORMONES ON NICOTINIC NEUROTRANSMISSION
PUJA, Giulia
2013
Abstract
Thyroid hormones (THs) play a crucial role for the correct functioning of the mammalian central nervous system. Their genomic actions are well known and recently the attention has been focused on their novel non-genomic effects as modulators of several neurotransmitter systems (Losi et al. 2008, Puia et. al 2011). Nicotinic acetylcholine receptors (nAChRs) are widely distributed throughout the brain and play important roles in regulating neuronal activity in several brain areas. By using the patch clamp technique in the whole cell configuration, we tested the effect of THs on nAChRs expressed in SHSY5Y neuroblastoma cells, in primary cultures of cortical neurons and in 293 HEK cell lines. In SHSY5Y, THs showed a dose-dependent reduction of nicotine (NIC) (10μM) current ( IC50 T3 10+/- 2 μM; IC50 T4 7+/- 2.5 μM). Their effect was not competitive and more pronounced at high agonist concentrations. Similar results were obtained using Acetylcholine (Ach) as agonist. THs reduced NIC current in cortical neurons even though their modulatory effects were variable and less marked. To test possible subunit specificity for T3 and T4 modulation, we analyze their effect in HEK293 cells expressing α4β2 nAChRs. T3 (1μM) reduced Ach (1μM)-evoked current of 32 +/- 9 % and T4 of 26 +/- 6 %. It's well known that several cognitive impairments have been resulted from THs deficiency and since “nicotinic circuits” are deeply implicated in learning and memory processes, is possible that also the reported non genomic effect of these hormones could regulate brain function.
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