Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/113553
Title: | Increased Synaptic ATP Release and CD73-Mediated Formation of Extracellular Adenosine in the Control of Behavioral and Electrophysiological Modifications Caused by Chronic Stress | Authors: | Dias, Liliana Pochmann, Daniela Lemos, Cristina Silva, Henrique B. Real, Joana I. Gonçalves, Francisco Q. Rial, Daniel Gonçalves, Nélio Simões, Ana Patrícia Ferreira, Samira G. Agostinho, Paula M. Cunha, Rodrigo A. Tomé, Ângelo R. |
Keywords: | ATP; adenosine; CD73; ecto-5′-nucleotidase; stress; hippocampus; prefrontal cortex; memory; mood; nerve terminals | Issue Date: | 5-Apr-2023 | Publisher: | American Chemical Society | Project: | info:eu-repo/grantAgreement/UIDB/04539/2020 CENTRO-01-0145- FEDER-000008 CENTRO-01-0246- FEDER-000010 SFRH/BD/147159/2019 |
Serial title, monograph or event: | ACS Chemical Neuroscience | Volume: | 14 | Issue: | 7 | Abstract: | Increased ATP release and its extracellular catabolism through CD73 (ecto-5'-nucleotidase) lead to the overactivation of adenosine A2A receptors (A2AR), which occurs in different brain disorders. A2AR blockade blunts mood and memory dysfunction caused by repeated stress, but it is unknown if increased ATP release coupled to CD73-mediated formation of extracellular adenosine is responsible for A2AR overactivation upon repeated stress. This was now investigated in adult rats subject to repeated stress for 14 consecutive days. Frontocortical and hippocampal synaptosomes from stressed rats displayed an increased release of ATP upon depolarization, coupled to an increased density of vesicular nucleotide transporters and of CD73. The continuous intracerebroventricular delivery of the CD73 inhibitor α,β-methylene ADP (AOPCP, 100 μM) during restraint stress attenuated mood and memory dysfunction. Slice electrophysiological recordings showed that restraint stress decreased long-term potentiation both in prefrontocortical layer II/III-layer V synapses and in hippocampal Schaffer fibers-CA1 pyramid synapses, which was prevented by AOPCP, an effect occluded by adenosine deaminase and by the A2AR antagonist SCH58261. These results indicate that increased synaptic ATP release coupled to CD73-mediated formation of extracellular adenosine contributes to mood and memory dysfunction triggered by repeated restraint stress. This prompts considering interventions decreasing ATP release and CD73 activity as novel strategies to mitigate the burden of repeated stress. | URI: | https://hdl.handle.net/10316/113553 | ISSN: | 1948-7193 1948-7193 |
DOI: | 10.1021/acschemneuro.2c00810 | Rights: | openAccess |
Appears in Collections: | FCTUC Ciências da Vida - Artigos em Revistas Internacionais FMUC Medicina - Artigos em Revistas Internacionais I&D CNC - Artigos em Revistas Internacionais |
Files in This Item:
Page view(s)
82
checked on Oct 16, 2024
Download(s)
25
checked on Oct 16, 2024
Google ScholarTM
Check
Altmetric
Altmetric
This item is licensed under a Creative Commons License