The impact of scopolamine pretreatment on 3-iodothyronamine (T1AM) effects on memory and pain in mice

Laurino, Annunziatina; Lucenteforte, Ersilia; Siena, Gaetano De; Raimondi, Laura

doi:10.1016/j.yhbeh.2017.07.003

Cited by 15 publications

(13 citation statements)

References 17 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the β-phenylethylamine-like structure affords T 1 AM the ability to bind with various members of GPCR superfamily and ion channels ( Chiellini et al, 2017 ; Khajavi et al, 2017 ). It is indeed claimed that T 1 AM interacts with α2a adrenergic receptors, β2-adrenergic receptors and muscarinic receptors ( Kleinau et al, 2011 ; Dinter et al, 2015a , b ; Laurino et al, 2016 , 2017 ). Notably, outside the CNS, T 1 AM has been found to differentially regulate insulin secretion through actions at TAAR1 and α2a adrenergic receptor ( Chiellini et al, 2017 ; Lehmphul et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine

et al. 2018

View full text Add to dashboard Cite

The trace amine-associated receptor 1 (TAAR1) is expressed by dopaminergic neurons, but the precise influence of trace amines upon their functional activity remains to be fully characterized. Here, we examined the regulation of tyrosine hydroxylase (TH) by tyramine and beta-phenylethylamine (β-PEA) compared to 3-iodothyronamine (T1AM). Immunoblotting and amperometry were performed in dorsal striatal slices from wild-type (WT) and TAAR1 knockout (KO) mice. T1AM increased TH phosphorylation at both Ser19 and Ser40, actions that should promote functional activity of TH. Indeed, HPLC data revealed higher rates of L-dihydroxyphenylalanine (DOPA) accumulation in WT animals treated with T1AM after the administration of a DOPA decarboxylase inhibitor. These effects were abolished both in TAAR1 KO mice and by the TAAR1 antagonist, EPPTB. Further, they were specific inasmuch as Ser845 phosphorylation of the post-synaptic GluA1 AMPAR subunit was unaffected. The effects of T1AM on TH phosphorylation at both Ser19 (CamKII-targeted), and Ser40 (PKA-phosphorylated) were inhibited by KN-92 and H-89, inhibitors of CamKII and PKA respectively. Conversely, there was no effect of an EPAC analog, 8-CPT-2Me-cAMP, on TH phosphorylation. In line with these data, T1AM increased evoked striatal dopamine release in TAAR1 WT mice, an action blunted in TAAR1 KO mice and by EPPTB. Mass spectrometry imaging revealed no endogenous T1AM in the brain, but detected T1AM in several brain areas upon systemic administration in both WT and TAAR1 KO mice. In contrast to T1AM, tyramine decreased the phosphorylation of Ser40-TH, while increasing Ser845-GluA1 phosphorylation, actions that were not blocked in TAAR1 KO mice. Likewise, β-PEA reduced Ser40-TH and tended to promote Ser845-GluA1 phosphorylation. The D1 receptor antagonist SCH23390 blocked tyramine-induced Ser845-GluA1 phosphorylation, but had no effect on tyramine- or β-PEA-induced Ser40-TH phosphorylation. In conclusion, by intracellular cascades involving CaMKII and PKA, T1AM, but not tyramine and β-PEA, acts via TAAR1 to promote the phosphorylation and functional activity of TH in the dorsal striatum, supporting a modulatory influence on dopamine transmission.

show abstract

Section: Discussionmentioning

confidence: 99%

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine

et al. 2018

View full text Add to dashboard Cite

show abstract

“…When administered to rodents, T1AM induces neurological and metabolic effects similar, but also opposite to those induced by T3. Among these, T1AM activates neuroprotective signaling including the activation of the AKT and PKA signaling [2,3]; it stimulates neuronal plasticity [4,5] and induces central-mediated reduction of body temperature without activating the brown adipose tissue [6][7][8]. Most of the pharmacological effects of T1AM, including the effect on body temperature, have been described following acute administration of the amine.…”

Section: Introductionmentioning

confidence: 99%

3-Iodothyronamine Affects Thermogenic Substrates’ Mobilization in Brown Adipocytes

Gencarelli

Laurino

Landucci

et al. 2020

Biology

Self Cite

View full text Add to dashboard Cite

We investigated the effect of 3-iodothyronamine (T1AM) on thermogenic substrates in brown adipocytes (BAs). BAs isolated from the stromal fraction of rat brown adipose tissue were exposed to an adipogenic medium containing insulin in the absence (M) or in the presence of 20 nM T1AM (M+T1AM) for 6 days. At the end of the treatment, the expression of p-PKA/PKA, p-AKT/AKT, p-AMPK/AMPK, p-CREB/CREB, p-P38/P38, type 1 and 3 beta adrenergic receptors (β1–β3AR), GLUT4, type 2 deiodinase (DIO2), and uncoupling protein 1 (UCP-1) were evaluated. The effects of cell conditioning with T1AM on fatty acid mobilization (basal and adrenergic-mediated), glucose uptake (basal and insulin-mediated), and ATP cell content were also analyzed in both cell populations. When compared to cells not exposed, M+T1AM cells showed increased p-PKA/PKA, p-AKT/AKT, p-CREB/CREB, p-P38/P38, and p-AMPK/AMPK, downregulation of DIO2 and β1AR, and upregulation of glycosylated β3AR, GLUT4, and adiponectin. At basal conditions, glycerol release was higher for M+T1AM cells than M cells, without any significant differences in basal glucose uptake. Notably, in M+T1AM cells, adrenergic agonists failed to activate PKA and lipolysis and to increase ATP level, but the glucose uptake in response to insulin exposure was more pronounced than in M cells. In conclusion, our results suggest that BAs conditioning with T1AM promote a catabolic condition promising to fight obesity and insulin resistance.

show abstract

“…Thyroid hormone and thyroid hormone metabolites, including 3iodothyronamine (T1AM) are endowed of neuroprotective features including memory stimulation and retrieval (Manni et al, 2013;Laurino et al, 2017;Chaalal et al, 2019), reduction of spinal cord injury (Lv et al, 2018;Shulz et al, 2017) and protection of hippocampal neuron cell death induced by kainic-acid (KA; Laurino et al, 2018a). In this latter model we recently reported that thyroid hormone and thyroid hormone metabolites activated hippocampal AKT and that this activation was responsible for the neuroprotective effect of the 3-iodothyroacetic acid (TA1), the main oxidative metabolite of T1AM produced ubiquitously.…”

Section: Introductionmentioning

confidence: 99%

N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide (EPPTB) prevents 3-iodothyronamine (T1AM)-induced neuroprotection against kainic acid toxicity

Landucci

Gencarelli

Mazzantini

et al. 2019

Neurochemistry International

Self Cite

View full text Add to dashboard Cite

Thyroid hormone and thyroid hormone metabolites, including 3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1), activate AKT signaling in hippocampal neurons affording protection from excitotoxic damage. We aim to explore whether the mechanism of T1AM neuroprotection against kainic acid (KA)-induced excitotoxicity included the activation of the trace amine associated receptor isoform 1 (TAAR1), one of T1AM targets. Rat organotypic hippocampal slices were exposed to vehicle (Veh) or to 5 μM kA for 24 h in the absence or presence of 0.1, 1 and 10 μM T1AM or to 0.1, 1 and 10 μM T1AM and 1 μM N-(3-Ethoxy-phenyl)-4-pyrrolidin-1yl-3-trifluoromethyl-benzamide (EPPTB), the only available TAAR1 antagonist, or to 1 μM T1AM in the absence or in the presence of 10 μM LY294002, an inhibitor of phosphoinositide 3-kinases (PI3Ks). Cell death was evaluated by measuring propidium iodide (PI) levels of fluorescence 24 h after treatment. In parallel, the expression levels of p-AKT and p-PKA were evaluated by Western blot analysis of slice lysates. The activity of mitochondrial monoamine oxidases (MAO) was assayed fluorimetrically. 24 h exposure of slices to T1AM resulted in the activation of AKT and PKA. KA exposure induced cell death in the CA3 region and significantly reduced p-AKT and p-PKA levels. The presence of 1 and 10 μM T1AM significantly protected neurons from death and conserved both kinase levels with the essential role of AKT in neuroprotection. Furthermore, EPPTB prevented T1AM-induced neuroprotection, activation of PKA and AKT. Of note, in the presence of EPPTB T1AM degradation by MAO was reduced. Our results indicate that the neuroprotection offered by T1AM depends, as for TA1, on AKT activation but do not allow to conclusively indicate TAAR1 as the target implicated.

show abstract

The impact of scopolamine pretreatment on 3-iodothyronamine (T1AM) effects on memory and pain in mice

Cited by 15 publications

References 17 publications

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine

Striatal Tyrosine Hydroxylase Is Stimulated via TAAR1 by 3-Iodothyronamine, But Not by Tyramine or β-Phenylethylamine

3-Iodothyronamine Affects Thermogenic Substrates’ Mobilization in Brown Adipocytes

N-(3-Ethoxy-phenyl)-4-pyrrolidin-1-yl-3-trifluoromethyl-benzamide (EPPTB) prevents 3-iodothyronamine (T1AM)-induced neuroprotection against kainic acid toxicity

Contact Info

Product

Resources

About