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Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS start long before motor symptoms onset

Rocha, Mariana C ; Pousinha, Paula A ; Correia, Alexandra M ; Sebastião, Ana M ; Ribeiro, Joaquim A Raoul, Cedric

PloS one, 2013-09, Vol.8 (9), p.e73846-e73846 [Periódico revisado por pares]

United States: Public Library of Science

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Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS start long before motor symptoms onset
Autor: Rocha, Mariana C ; Pousinha, Paula A ; Correia, Alexandra M ; Sebastião, Ana M ; Ribeiro, Joaquim A
Raoul, Cedric
Assuntos: Acetylcholine ; Age ; Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - genetics ; Amyotrophic Lateral Sclerosis - pathology ; Amyotrophic Lateral Sclerosis - physiopathology ; Animals ; Calcium (intracellular) ; Degeneration ; Denervation ; Deregulation ; Diaphragm ; Diaphragm (anatomy) ; Diaphragm - innervation ; Diaphragm - metabolism ; Disease Models, Animal ; Female ; Females ; Genetic engineering ; Humans ; Hypotheses ; Innervation ; Laboratories ; Male ; Males ; Medicine ; Mice ; Mice, Transgenic ; Motor Activity - genetics ; Motor Activity - physiology ; Motor neurons ; Muscle, Skeletal - innervation ; Muscle, Skeletal - metabolism ; Muscles ; Musculoskeletal system ; Mutation ; Nerve endings ; Neuromuscular Junction - metabolism ; Neuromuscular Junction - physiology ; Neuromuscular junctions ; Neuromuscular transmission ; Neurosciences ; Pharmacology ; Pyramidal tracts ; Rodents ; Superoxide dismutase ; Superoxide Dismutase - genetics ; Superoxide Dismutase - metabolism ; Synaptic cleft ; Synaptic Potentials - genetics ; Synaptic Potentials - physiology ; Synaptic transmission ; Synaptic Transmission - genetics ; Synaptic Transmission - physiology ; Time Factors ; Transgenic animals ; Transgenic mice
É parte de: PloS one, 2013-09, Vol.8 (9), p.e73846-e73846
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
Competing Interests: The authors have declared that no competing interests exist.
Current address: Institute for Ageing and Health, Centre for Brain Ageing and Vitality, Mitochondrial Research Group, Newcastle Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
Conceived and designed the experiments: PAP MCR JAR AMC AMS. Performed the experiments: MCR. Analyzed the data: MCR PAP. Wrote the manuscript: MCR PAP JAR AMC AMS.
Current address: Institut de Pharmacologie Moléculaire et Cellulaire UMR7275 CNRS, Equipe Mécanismes moléculaires de la plasticité neuronale physiologique et pathologique, Sophia-Antipolis, Valbonne, France
Descrição: Amyotrophic lateral sclerosis is characterized by a progressive degeneration of the corticospinal tract motor neurons. Growing evidence suggests that degeneration may begin at the distal axon proceeding in a dying-back pattern. It seemed therefore of interest to investigate synaptic transmission at the neuromuscular junction (NMJ) in pre- and symptomatic phases of the disease. Endplate potentials (EPPs), miniatures endplate potentials (MEPPs) and giant MEPPs (GMEPPs) were recorded from innervated diaphragm muscle fibers from 4-6 and 12-15 weeks-old SOD1(G93A) mice and non-transgenic aged-matched littermates (WT). In the pre-symptomatic phase, SOD1(G93A) mice exhibited a significant increase in the mean amplitude of EPPs together with an increase in the mean quantal content of EPPs, suggesting that more acetylcholine is being released into the synaptic cleft. SOD1(G93A) mice presented a higher frequency of GMEPPs, suggestive of intracellular Ca(2+) deregulation in nerve terminals. The increase in the mean amplitude of MEPPs and the decreased mean rise-time of MEPPs in SOD1(G93A) mice point to post-synaptic related changes. In the symptomatic phase, electrophysiological data showed evidence for two NMJ groups in SOD1(G93A) mice: SOD1a and SOD1b. SOD1a group presented reduced mean amplitude of both EPPs and MEPPs. The mean rise-time of MEPPs was increased, when compared to WT and to SOD1b group, indicating impairments in the neuromuscular transmission. In contrast, the neuromuscular transmission of SOD1b group was not different from age-matched WT nor pre-symptomatic SOD1(G93A) mice, being somehow in between both groups. Altogether these results show that the neuromuscular transmission of SOD1(G93A) mice is enhanced in the pre-symptomatic phase. In the symptomatic phase our results are consistent with the hypothesis that the diaphragm of SOD1(G93A) mice is undergoing cycles of denervation/re-innervation supported by mixed neuromuscular junction populations. These early changes in the neuromuscular transmission of SOD1(G93A) mice suggest that the ALS associated events start long before symptoms onset.
Editor: United States: Public Library of Science
Idioma: Inglês

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Early changes of neuromuscular transmission in the SOD1(G93A) mice model of ALS start long before motor symptoms onset

Rocha, Mariana C ; Pousinha, Paula A ; Correia, Alexandra M ; Sebastião, Ana M ; Ribeiro, Joaquim A Raoul, Cedric

United States: Public Library of Science

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