Hippocampal synaptic dysfunction in the SOD1 G93A mouse model of Amyotrophic Lateral Sclerosis: Reversal by adenosine A 2A R blockade.

Autor: Rei N; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal., Rombo DM; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal., Ferreira MF; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal., Baqi Y; Department of Chemistry, Faculty of Science, Sultan Qaboos University, PO Box 36, Postal Code 123, Muscat, Oman., Müller CE; Pharma-Zentrum Bonn, Pharmazeutisches Institut, Pharmazeutische Chemie I, University of Bonn, Germany., Ribeiro JA; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal., Sebastião AM; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal., Vaz SH; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Portugal; Instituto de Farmacologia e Neurociências, Faculdade de Medicina, Universidade de Lisboa, Portugal. Electronic address: svaz@medicina.ulisboa.pt.
Jazyk: angličtina
Zdroj: Neuropharmacology [Neuropharmacology] 2020 Jul; Vol. 171, pp. 108106. Date of Electronic Publication: 2020 Apr 18.
DOI: 10.1016/j.neuropharm.2020.108106
Abstrakt: Amyotrophic Lateral Sclerosis (ALS) mostly affects motor neurons, but non-motor neural and cognitive alterations have been reported in ALS mouse models and patients. Here, we evaluated if time-dependent biphasic changes in synaptic transmission and plasticity occur in hippocampal synapses of ALS SOD1 G93A mice. Recordings were performed in hippocampal slices of SOD1 G93A and age-matched WT mice, in the pre-symptomatic and symptomatic stages. We found an enhancement of pre-synaptic function and increased adenosine A 2A receptor levels in the hippocampus of pre-symptomatic mice. In contrast, in symptomatic mice, there was an impairment of long-term potentiation (LTP) and a decrease in NMDA receptor-mediated synaptic currents, with A 2A R levels also being increased. Chronic treatment with the A 2A R antagonist KW-6002, rescued LTP and A 2A R values. Altogether, these findings suggest an increase in synaptic function during the pre-symptomatic stage, followed by a decrease in synaptic plasticity in the symptomatic stage, which involves over-activation of A 2A R from early disease stages.
Competing Interests: Declaration of competing interest The authors declare no competing interests.
(Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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