Neuromuscular transmission modulation by adenosine upon aging

Pousinha, Paula A.; Correia, Alexandra Marçal; Sebastião, Ana M.; Ribeiro, Joaquim A.

doi:10.1016/j.neurobiolaging.2012.01.008

Cited by 11 publications

(14 citation statements)

References 36 publications

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“…Interestingly, we could observe some similarities between the symptomatic SOD1(G93A) mice (herein presented) and aged rats (70–80 weeks old; [18]) in what respects to the effect of the A 2A receptor selective agonist, CGS21680. In both cases there is an absence of effect of A 2A receptors.…”

Section: Discussionsupporting

confidence: 51%

“…Though the selective A 2A receptor agonist CGS 21680 [17] has been extensively used in research, namely at the neuromuscular junction [9], [13], [18], there are only few studies reporting its effects at the mouse neuromuscular junction, the existing being on K + -evoked ACh-release (e.g. [19]).…”

Section: Resultsmentioning

confidence: 99%

“…In addition, multiple interactions of A 2A receptors with other proteins have been described both in peripheral and central nervous system [8]. At the neuromuscular junction, A 2A receptors are known to interact with adenosine A 1 receptors [13], [18], [27], presynaptic nicotinic autofacilitatory receptors [28], tyrosin receptor kinase B (TrkB) [29] or calcitonin gene-related peptide [30]. Furthermore, SOD1(G93A) mice pathogenesis is characterized by increased oxidative stress [2] and A 2A receptors present redox-sensitive synchronizing action at the neuromuscular synapse [31].…”

Section: Discussionmentioning

confidence: 99%

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Adenosine A2A Receptors Activation Facilitates Neuromuscular Transmission in the Pre-Symptomatic Phase of the SOD1(G93A) ALS Mice, but Not in the Symptomatic Phase

et al. 2014

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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.

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Section: Discussionsupporting

confidence: 51%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Adenosine A2A Receptors Activation Facilitates Neuromuscular Transmission in the Pre-Symptomatic Phase of the SOD1(G93A) ALS Mice, but Not in the Symptomatic Phase

et al. 2014

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“…Additionally, it has been shown in rats that aging differentially affects adenosine receptor pre-synaptic modulation of neuromuscular transmission. Specifically, the excitatory influence on neuromuscular transmission seems to decrease with age, while the inhibitory effects remain unchanged (Pousinha et al, 2012).…”

Section: Discussionmentioning

confidence: 97%

Increased motor unit potential shape variability across consecutive motor unit discharges in the tibialis anterior and vastus medialis muscles of healthy older subjects

Hourigan

McKinnon

Johnson

et al. 2015

Clinical Neurophysiology

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“…Intracellular recordings were performed in the conventional way [14–16]. Glass microelectrodes (10-20 MΩ) filled with 3M KCl were inserted within muscle fibers at the motor endplate and the reference electrode was an Ag–AgCl pellet placed in the bath.…”

Section: Methodsmentioning

confidence: 99%

Early Changes of Neuromuscular Transmission in the SOD1(G93A) Mice Model of ALS Start Long before Motor Symptoms Onset

et al. 2013

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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 Ca2+ 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.

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Neuromuscular transmission modulation by adenosine upon aging

Cited by 11 publications

References 36 publications

Adenosine A2A Receptors Activation Facilitates Neuromuscular Transmission in the Pre-Symptomatic Phase of the SOD1(G93A) ALS Mice, but Not in the Symptomatic Phase

Adenosine A2A Receptors Activation Facilitates Neuromuscular Transmission in the Pre-Symptomatic Phase of the SOD1(G93A) ALS Mice, but Not in the Symptomatic Phase

Increased motor unit potential shape variability across consecutive motor unit discharges in the tibialis anterior and vastus medialis muscles of healthy older subjects

Early Changes of Neuromuscular Transmission in the SOD1(G93A) Mice Model of ALS Start Long before Motor Symptoms Onset

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