Nov 12, 2019

Exogenous 3-Iodothyronamine Rescues the Entorhinal Cortex from β -Amyloid Toxicity

Thyroid : Official Journal of the American Thyroid Association
Alice AccorroniNicola Origlia

Abstract

Background: A novel form of thyroid hormone (TH) signaling is represented by 3-iodothyronamine (T1AM), an endogenous TH derivative that interacts with specific molecular targets, including trace amine-associated receptor 1 (TAAR1), and induces pro-learning and anti-amnestic effects in mice. Dysregulation of TH signaling has long been hypothesized to play a role in Alzheimer's disease (AD). In the present investigation, we explored the neuroprotective role of T1AM in beta amyloid (Aβ)-induced synaptic and behavioral impairment, focusing on the entorhinal cortex (EC), an area that is affected early by AD pathology. Methods: Field potentials were evoked in EC layer II, and long-term potentiation (LTP) was elicited by high frequency stimulation (HFS). T1AM (5 μM) and/or Aβ(1-42) (200 nM), were administered for 10 minutes, starting 5 minutes before HFS. Selective TAAR1 agonist RO5166017 (250 nM) and TAAR1 antagonist EPPTB (5 nM) were also used. The electrophysiological experiments were repeated in EC-slices taken from a mouse model of AD (mutant human amyloid precursor protein [mhAPP], J20 line). We also assessed the in vivo effects of T1AM on EC-dependent associative memory deficits, which were detected in mhAPP mice by behavior...Continue Reading

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Citations

Mentioned in this Paper

Study
In Vivo
Western Blotting
Memory Impairment
Action Potentials
Administration Procedure
Alzheimer's Disease
Evaluation
Thyroid Hormone Mediated Signaling Pathway
Mass Spectrometry

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