Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.

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 neuromu...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Filipe Nascimento, Paula A Pousinha, Alexandra M Correia, Rui Gomes, Ana M Sebastião, Joaquim A Ribeiro
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/aef35ee0f28541f599f8e8ed3f92f0a2
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:aef35ee0f28541f599f8e8ed3f92f0a2
record_format	dspace
spelling	oai:doaj.org-article:aef35ee0f28541f599f8e8ed3f92f0a22021-11-25T06:05:55ZAdenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.1932-620310.1371/journal.pone.0104081https://doaj.org/article/aef35ee0f28541f599f8e8ed3f92f0a22014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25093813/?tool=EBIhttps://doaj.org/toc/1932-6203Amyotrophic 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.Filipe NascimentoPaula A PousinhaAlexandra M CorreiaRui GomesAna M SebastiãoJoaquim A RibeiroPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 8, p e104081 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Filipe Nascimento Paula A Pousinha Alexandra M Correia Rui Gomes Ana M Sebastião Joaquim A Ribeiro Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
description	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.
format	article
author	Filipe Nascimento Paula A Pousinha Alexandra M Correia Rui Gomes Ana M Sebastião Joaquim A Ribeiro
author_facet	Filipe Nascimento Paula A Pousinha Alexandra M Correia Rui Gomes Ana M Sebastião Joaquim A Ribeiro
author_sort	Filipe Nascimento
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.
title_short	Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
title_full	Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
title_fullStr	Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
title_full_unstemmed	Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.
title_sort	adenosine a2a receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the sod1(g93a) als mice, but not in the symptomatic phase.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/aef35ee0f28541f599f8e8ed3f92f0a2
work_keys_str_mv	AT filipenascimento adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase AT paulaapousinha adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase AT alexandramcorreia adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase AT ruigomes adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase AT anamsebastiao adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase AT joaquimaribeiro adenosinea2areceptorsactivationfacilitatesneuromusculartransmissioninthepresymptomaticphaseofthesod1g93aalsmicebutnotinthesymptomaticphase
_version_	1718414182921011200

Adenosine A2A receptors activation facilitates neuromuscular transmission in the pre-symptomatic phase of the SOD1(G93A) ALS mice, but not in the symptomatic phase.

Ejemplares similares