title: Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
abstract: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease leading to motor neuron dysfunction resulting in impairment of neuromuscular transmission. A2A adenosine receptors have already been considered as a potential therapeutical target for ALS but their neuromodulatory role at the neuromuscular junction in ALS remains to be clarified. In the present work, we evaluated the effects of A2A receptors on neuromuscular transmission of an animal model of ALS: SOD1(G93A) mice either in the pre-symptomatic (4-6 weeks old) or in the symptomatic (12-14 weeks old) stage. Electrophysiological experiments were performed obtaining intracellular recordings in Mg2+ paralyzed phrenic nerve-hemidiaphragm preparations. Endplate potentials (EPPs), quantal content (q. c.) of EPPs, miniature endplate potentials (MEPPs) and giant miniature endplate potential (GMEPPs) were recorded. In the pre-symptomatic phase of the disease (4-6 weeks old mice), the selective A2A receptor agonist, CGS 21680, significantly enhanced (p<0.05 Unpaired t-test) the mean amplitude and q.c. of EPPs, and the frequency of MEPPs and GMEPPs at SOD1(G93A) neuromuscular junctions, the effect being of higher magnitude (p<0.05, Unpaired t-test) than age-matched control littermates. On the contrary, in symptomatic mice (12-14 weeks old), CGS 21680 was devoid of effect on both the amplitude and q.c. of EPPs and the frequency of MEPPs and GMEPPs (p<0.05 Paired t-test). The results herein reported clearly document that at the neuromuscular junction of SOD1(G93A) mice there is an exacerbation of A2A receptor-mediated excitatory effects at the pre-symptomatic phase, whereas in the symptomatic phase A2A receptor activation is absent. The results thus suggest that A2A receptors function changes with ALS progression.
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
authors.forename: Filipe
authors.initials: F
authors.lastname: Nascimento
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Pousinha
authors.affiliation: Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal; National Museum of Natural History and Science, University of Lisbon, Lisbon, Portugal.
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Correia
authors.affiliation: Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal; Faculty of Sciences, University of Lisbon, Lisbon, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Gomes
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Sebastião
authors.affiliation: Institute of Pharmacology and Neurosciences, Faculty of Medicine, University of Lisbon, Lisbon, Portugal; Unit of Neurosciences, Instituto de Medicina Molecular, University of Lisbon, Lisbon, Portugal.
authors.forename: Joaquim A
authors.initials: JA
authors.lastname: Ribeiro
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D000818:Animals; D018450:Disease Progression; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006801:Humans; D008297:Male; D008822:Mice, Transgenic; D009045:Motor Endplate / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000473:pathology / Q000503:physiopathology*; D010627:Phenethylamines; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D010627:Phenethylamines; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D013482:Superoxide Dismutase; D000241:Adenosine
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