Show simple item record

dc.contributor.authorCerveró Cebrià, Clàudia
dc.contributor.authorMontull, Neus
dc.contributor.authorTarabal Mostazo, Olga
dc.contributor.authorPiedrafita Llorens, Lídia
dc.contributor.authorEsquerda Colell, Josep
dc.contributor.authorCalderó i Pardo, Jordi
dc.date.accessioned2017-04-21T14:38:25Z
dc.date.issued2016
dc.identifier.issn1933-7213
dc.identifier.urihttp://hdl.handle.net/10459.1/59522
dc.description.abstractSpinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by spinal and brainstem motor neuron (MN) loss and skeletal muscle paralysis. Currently there is no effective treatment other than supportive care to ameliorate the quality of life of SMA patients. Some studies have reported that physical exercise is potentially beneficial in SMA by improving muscle strength and motor function. The AMP-activated protein kinase (AMPK) agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) has been reported to be an exercise mimetic agent that is able to regulate muscle metabolism and increase endurance both at rest and during exercise. Chronic AICAR administration has been shown to ameliorate the dystrophic muscle phenotype and motor behavior in the mdx mouse, a model of Duchenne muscular dystrophy. Here, we investigated whether chronic AICAR treatment was able to elicit beneficial effects on motor abilities and neuromuscular histopathology in a mouse model of severe SMA (the SMNΔ7 mouse). We report that AICAR improved skeletal muscle atrophy and structural changes found in neuromuscular junctions of SMNΔ7 animals. However, although AICAR prevented the loss of glutamatergic excitatory synapses on MNs, this compound was not able to mitigate MN loss or the microglial and astroglial reaction occurring in the spinal cord of diseased mice. Moreover, no improvement in both survival and motor performance was seen in SMNΔ7 animals treated with AICAR. The beneficial effects of AICAR in SMA found in our study are SMN-independent, since no changes in the expression of this protein were seen in the spinal cord and skeletal muscle of diseased animals treated with this compound.
dc.description.sponsorshipThis work was supported by grants from the Ministerio de Economía y Competitividad cofinanced by FEDER (SAF2012-31831 to J.C., and SAF2011-22908 to J.E.E.)
dc.format.mimetypeapplication/pdf
dc.language.isoeng
dc.publisherSpringer Verlag
dc.relationMICINN/PN2008-2011/SAF2012-31831
dc.relationMICINN/PN2008-2011/SAF2011-22908
dc.relation.isformatofReproducció del document publicat a: https://doi.org/10.1007/s13311-015-0399-x
dc.relation.ispartofNeurotherapeutics, 2016, vol. 13, p. 198-216
dc.rights(c) American Society for Experimental NeuroTherapeutics, 2016
dc.subjectAICAR
dc.subjectspinal muscular atrophy
dc.subjectskeletal muscle
dc.subjectNeuromuscular junction
dc.subjectspinal cord ventral horn
dc.subject.classificationAtròfia muscular
dc.subject.classificationMedul·la espinal
dc.subject.classificationUnió neuromuscular
dc.subject.otherMuscular atrophy
dc.subject.otherSpinal cord
dc.subject.otherMyoneural junction
dc.titleChronic treatment with the AMPA agonist AICAR prevents skeletal muscle pathology but fails to improve clinical outcome in a mouse model of severe spinal muscular atrophy
dc.typeinfo:eu-repo/semantics/article
dc.date.updated2017-04-21T14:38:26Z
dc.identifier.idgrec023438
dc.type.versioninfo:eu-repo/semantics/publishedVersion
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccess
dc.identifier.doihttps://doi.org/10.1007/s13311-015-0399-x
dc.date.embargoEndDate2025-01-01


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record