Shared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Muscles

dc.contributor.authorValdez, Gregorioen
dc.contributor.authorTapia, Juan C.en
dc.contributor.authorLichtman, Jeff W.en
dc.contributor.authorFox, Michael A.en
dc.contributor.authorSanes, Joshua R.en
dc.date.accessioned2017-02-13T13:27:28Zen
dc.date.available2017-02-13T13:27:28Zen
dc.date.issued2012-04-02en
dc.description.abstractNormal aging and neurodegenerative diseases both lead to structural and functional alterations in synapses. Comparison of synapses that are generally similar but respond differently to insults could provide the basis for discovering mechanisms that underlie susceptibility or resistance to damage. Here, we analyzed skeletal neuromuscular junctions (NMJs) in 16 mouse muscles to seek such differences. We find that muscles respond in one of three ways to aging. In some, including most limb and trunk muscles, age-related alterations to NMJs are progressive and extensive during the second postnatal year. NMJs in other muscles, such as extraocular muscles, are strikingly resistant to change. A third set of muscles, including several muscles of facial expression and the external anal sphinter, succumb to aging but not until the third postnatal year. We asked whether susceptible and resistant muscles differed in rostrocaudal or proximodistal position, source of innervation, motor unit size, or fiber type composition. Of these factors, muscle innervation by brainstem motor neurons correlated best with resistance to age-related decline. Finally, we compared synaptic alterations in normally aging muscles to those in a mouse model of amyotrophic lateral sclerosis (ALS). Patterns of resistance and susceptibility were strikingly correlated in the two conditions. Moreover, damage to NMJs in aged muscles correlated with altered expression and distribution of CRMP4a and TDP-43, which are both altered in motor neurons affected by ALS. Together, these results reveal novel structural, regional and molecular parallels between aging and ALS.en
dc.description.versionPublished versionen
dc.format.extent? - ? (17) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0034640en
dc.identifier.issn1932-6203en
dc.identifier.issue4en
dc.identifier.urihttp://hdl.handle.net/10919/75002en
dc.identifier.volume7en
dc.languageEnglishen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000304780500057&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectamyotrophic-lateral-sclerosisen
dc.subjectfrontotemporal lobar degenerationen
dc.subjectage-related-changesen
dc.subjectneurodegenerative diseasesen
dc.subjectextraocular-musclesen
dc.subjectsuperoxide-dismutaseen
dc.subjectaxonal-transporten
dc.subjecttransgenic miceen
dc.subjectmotor-neuronsen
dc.subjectonufs nucleusen
dc.titleShared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Musclesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/Faculty of Health Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Instituteen
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