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T1AM-TAAR1 signalling protects against OGD-induced synaptic dysfunction in the entorhinal cortex
- Source :
- Neurobiology of Disease, Vol 151, Iss, Pp 105271-(2021)
- Publication Year :
- 2021
- Publisher :
- Elsevier, 2021.
-
Abstract
- Abnormalities in thyroid hormones (TH) availability and/or metabolism have been hypothesized to contribute to Alzheimer's disease (AD) and to be a risk factor for stroke. Recently, 3-iodothyronamine (T1AM), an endogenous amine putatively derived from TH metabolism, gained interest for its ability to promote learning and memory in the mouse. Moreover, T1AM has been demonstrated to rescue the β-Amyloid dependent LTP impairment in the entorhinal cortex (EC), a brain area crucially involved in learning and memory and early affected during AD. In the present work, we have investigated the effect of T1AM on ischemia-induced EC synaptic dysfunction. In EC brain slices exposed to oxygen-glucose deprivation (OGD), we demonstrated that the acute perfusion of T1AM (5 μM) was capable of preventing ischemia-induced synaptic depression and that this protective effect was mediated by the trace amine-associated receptor 1 (TAAR1). Moreover, we demonstrated that activation of the BDNF-TrkB signalling is required for T1AM action during ischemia. The protective effect of T1AM was more evident when using EC slices from transgenic mutant human APP (mhAPP mice) that are more vulnerable to the effect of OGD. Our results confirm that the TH derivative T1AM can rescue synaptic function after transient ischemia, an effect that was also observed in a Aβ-enriched environment.
- Subjects :
- 0301 basic medicine
3-iodothyronamine
Ischemia
Endogeny
lcsh:RC321-571
3-Iodothyronamine
Synaptic depression
03 medical and health sciences
chemistry.chemical_compound
Trace amine-associated receptor 1
0302 clinical medicine
TAAR1
medicine
Receptor
Brain derived neurotrophic factor
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Entorhinal cortex
Brain-derived neurotrophic factor
Alzheimer's disease
business.industry
Long-term potentiation
medicine.disease
030104 developmental biology
Neurology
chemistry
business
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Volume :
- 151
- Database :
- OpenAIRE
- Journal :
- Neurobiology of Disease
- Accession number :
- edsair.doi.dedup.....36f951d1f33591d1ebe4318df80cdac7