Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/101263
Title: Adenosine A2A receptors format long-term depression and memory strategies in a mouse model of Angelman syndrome
Authors: Moreira-de-Sá, Ana 
Gonçalves, Francisco Q. 
Lopes, João P. 
Silva, Henrique B. 
Tomé, Ângelo R. 
Cunha, Rodrigo A. 
Canas, Paula 
Keywords: Adenosine A(2A) receptor; Angelman syndrome; Hippocampus; Mouse model; Synaptic plasticity; Ube3a
Issue Date: 2020
Project: Fundação Amélia de Mello 
CENTRO-01-0145-FEDER-000008:BrainHealth 2020 
CENTRO-01-0246-FEDER-000010 
POCI-01-0145-FEDER-031274 
info:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB/04539/2020/PT 
Serial title, monograph or event: Neurobiology of Disease
Volume: 146
Abstract: Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally inherited Ube3a neuronal protein, whose main features comprise severe intellectual disabilities and motor impairments. Previous studies with the Ube3am-/p+ mouse model of AS revealed deficits in synaptic plasticity and memory. Since adenosine A2A receptors (A2AR) are powerful modulators of aberrant synaptic plasticity and A2AR blockade prevents memory dysfunction in various brain diseases, we tested if A2AR could control deficits of memory and hippocampal synaptic plasticity in AS. We observed that Ube3am-/p+ mice were unable to resort to hippocampal-dependent search strategies when tested for learning and memory in the Morris water maze; this was associated with a decreased magnitude of long-term depression (LTD) in CA1 hippocampal circuits. There was an increased density of A2AR in the hippocampus of Ube3am-/p+ mice and their chronic treatment with the selective A2AR antagonist SCH58261 (0.1 mg/kg/day, ip) restored both hippocampal-dependent learning strategies, as well as LTD deficits. Altogether, this study provides the first evidence of a role of A2AR as a new prospective therapeutic target to manage learning deficits in AS.
URI: https://hdl.handle.net/10316/101263
ISSN: 09699961
DOI: 10.1016/j.nbd.2020.105137
Rights: openAccess
Appears in Collections:I&D CNC - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
FCTUC Ciências da Vida - Artigos em Revistas Internacionais

Files in This Item:
File Description SizeFormat
1-s2.0-S0969996120304125-main.pdf2.37 MBAdobe PDFView/Open
Show full item record

SCOPUSTM   
Citations

12
checked on Apr 22, 2024

WEB OF SCIENCETM
Citations

12
checked on Apr 2, 2024

Page view(s)

92
checked on Apr 16, 2024

Download(s)

28
checked on Apr 16, 2024

Google ScholarTM

Check

Altmetric

Altmetric


This item is licensed under a Creative Commons License Creative Commons