Hippocampal synaptic dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis: Reversal by adenosine A2AR blockade

N. Rei, D. M. Rombo, M. F. Ferreira, Y. Baqi, C. E. Müller, J. A. Ribeiro, A. M. Sebastião, S. H. Vaz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


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 SOD1G93A mice. Recordings were performed in hippocampal slices of SOD1G93A and age-matched WT mice, in the pre-symptomatic and symptomatic stages. We found an enhancement of pre-synaptic function and increased adenosine A2A 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 A2AR levels also being increased. Chronic treatment with the A2AR antagonist KW-6002, rescued LTP and A2AR 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 A2AR from early disease stages.

Original languageEnglish
Article number108106
Publication statusPublished - Jul 2020


  • A receptor
  • ALS
  • Hippocampus
  • KW-6002
  • Long-term potentiation (LTP)
  • Neuronal plasticity
  • NMDA receptor

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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