T1AM-TAAR1 signalling protects against OGD-induced synaptic dysfunction in the entorhinal cortex

NEUROBIOLOGY OF DISEASE

卷:151

Article

Tozzi, Francesca¹  Rutigliano, Grazia²  Borso, Marco²  Falcicchia, Chiara³  Zucchi, Riccardo²  Origlia, Nicola³ 

[1] Scuola Normale Super Pisa, Bio SNS Lab, I-56124 Pisa, Italy

[2] Univ Pisa, Dept Pathol, I-56100 Pisa, Italy

[3] Italian Natl Res Council CNR, Inst Neurosci, Via Moruzzi 1, I-56124 Pisa, Italy

关键词: 3-iodothyronamine;    Trace amine-associated receptor 1;    Synaptic depression;    Ischemia;    Entorhinal cortex;    Brain derived neurotrophic factor;    Alzheimer's disease;   

DOI  :  10.1016/j.nbd.2021.105271

来源: Elsevier

【 摘 要 】

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 beta-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 mu M) 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 A beta-enriched environment.