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dc.contributor.authorValdez, Gregorioen_US
dc.contributor.authorTapia, Juan C.en_US
dc.contributor.authorLichtman, Jeff W.en_US
dc.contributor.authorFox, Michael A.en_US
dc.contributor.authorSanes, Joshua R.en_US
dc.date.accessioned2017-02-13T13:27:28Z
dc.date.available2017-02-13T13:27:28Z
dc.date.issued2012-04-02en_US
dc.identifier.issn1932-6203en_US
dc.identifier.urihttp://hdl.handle.net/10919/75002
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_US
dc.format.extent? - ? (17) page(s)en_US
dc.languageEnglishen_US
dc.publisherPLOSen_US
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_US
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectMultidisciplinary Sciencesen_US
dc.subjectScience & Technology - Other Topicsen_US
dc.subjectMULTIDISCIPLINARY SCIENCESen_US
dc.subjectAMYOTROPHIC-LATERAL-SCLEROSISen_US
dc.subjectFRONTOTEMPORAL LOBAR DEGENERATIONen_US
dc.subjectAGE-RELATED-CHANGESen_US
dc.subjectNEURODEGENERATIVE DISEASESen_US
dc.subjectEXTRAOCULAR-MUSCLESen_US
dc.subjectSUPEROXIDE-DISMUTASEen_US
dc.subjectAXONAL-TRANSPORTen_US
dc.subjectTRANSGENIC MICEen_US
dc.subjectMOTOR-NEURONSen_US
dc.subjectONUFS NUCLEUSen_US
dc.titleShared Resistance to Aging and ALS in Neuromuscular Junctions of Specific Musclesen_US
dc.typeArticle - Refereed
dc.description.versionPublished (Publication status)en_US
dc.title.serialPLOS ONEen_US
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0034640
dc.identifier.volume7en_US
dc.identifier.issue4en_US
pubs.organisational-group/Virginia Tech
pubs.organisational-group/Virginia Tech/All T&R Faculty
pubs.organisational-group/Virginia Tech/Faculty of Health Sciences
pubs.organisational-group/Virginia Tech/University Research Institutes
pubs.organisational-group/Virginia Tech/University Research Institutes/Virginia Tech Carilion Research Institute


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Creative Commons Attribution 4.0 International
License: Creative Commons Attribution 4.0 International