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

Hippocampal synaptic dysfunction in the SOD1G93A mouse model of Amyotrophic Lateral Sclerosis: Reversal by adenosine A2AR blockade. Neuropharmacology. 2020 Apr 17;:108106 Authors: N R, Rombo DM, Ferreira MF, Baqi Y, Müller CE, Ribeiro JA, Sebastião AM, Vaz SH Abstract 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. PMID: 32311420 [PubMed - as supplied by publisher]
Source: Neuropharmacology - Category: Drugs & Pharmacology Authors: Tags: Neuropharmacology Source Type: research