May 11, 2019

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

Neurochemistry International
Elisa LanducciLaura Raimondi

Abstract

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-1-yl-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 t...Continue Reading

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Mentioned in this Paper

M Protein, multiple myeloma
AKT1
Western Blotting
Tissue Damage
Neurons
Propidium Iodide
Cessation of Life
TAAR1 protein, human
Neuroprotection
N-(3-ethoxyphenyl)-4-pyrrolidin-1-yl-3-trifluoromethylbenzamide

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