{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T11:16:05Z","timestamp":1764587765183},"reference-count":42,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PEst\u2010C\/SAU\/UI3282\/2013","UID\/NEU\/04539\/2013","COMPETE\u2010FEDER","EXPL\/DTP\u2010DES\/0104\/2013","SFRH\/BD\/78166\/2011"],"award-info":[{"award-number":["PEst\u2010C\/SAU\/UI3282\/2013","UID\/NEU\/04539\/2013","COMPETE\u2010FEDER","EXPL\/DTP\u2010DES\/0104\/2013","SFRH\/BD\/78166\/2011"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2016,5]]},"abstract":"Summary<\/jats:title>Aims<\/jats:title>Astrocytic S100B and receptor for advanced glycation endproducts (RAGE<\/jats:styled-content>) have been implicated in Parkinson\u05f3s disease (PD<\/jats:styled-content>) pathogenesis through yet unclear mechanisms. This study attempted to characterize S100B\/mRAGE<\/jats:styled-content> (signaling isoform) axis in a dying\u2010back dopaminergic (DA<\/jats:styled-content>ergic) axonopathy setting, which mimics an early event of PD<\/jats:styled-content> pathology.<\/jats:p><\/jats:sec>Methods<\/jats:title>C57BL<\/jats:styled-content>\/6 mice were submitted to a chronic MPTP<\/jats:styled-content> paradigm (20\u00a0mg\/kg i.p., 2 i.d\u201012\u00a0h apart, 5\u00a0days\/week for 2\u00a0weeks) and euthanized 7\u00a0days posttreatment to assess mRAGE<\/jats:styled-content> cellular distribution and S100B\/mRAGE<\/jats:styled-content> density in striatum, after probing their locomotor activity (pole test and rotarod). Dopaminergic status, oxidative stress, and gliosis were also measured (HPLC<\/jats:styled-content>\u2010ED<\/jats:styled-content>, WB<\/jats:styled-content>, IHC<\/jats:styled-content>).<\/jats:p><\/jats:sec>Results<\/jats:title>This MPTP<\/jats:styled-content> regimen triggered increased oxidative stress (augmented HNE<\/jats:styled-content> levels), gliosis (GS<\/jats:styled-content>\/Iba1\u2010reactive morphology), loss of DA<\/jats:styled-content>ergic fibers (decreased tyrosine hydroxylase levels), and severe hypodopaminergia. Biochemical deficits were not translated into motor abnormalities, mimicking a presymptomatic PD<\/jats:styled-content> period. Remarkably, striatal neurotrophic S100B\/mRAGE<\/jats:styled-content> levels and major neuronal mRAGE<\/jats:styled-content> localization coexist with compensatory responses (3\u2010fold increase in DA<\/jats:styled-content> turnover), which are important to maintain normal motor function.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Our findings rule out the involvement of S100B\/mRAGE<\/jats:styled-content> axis in striatal reactive gliosis, DA<\/jats:styled-content>ergic axonopathy and warrant further exploration of its neurotrophic effects in a presymptomatic compensatory PD<\/jats:styled-content> stage, which is a fundamental period for successful implementation of therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.12508","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T10:41:54Z","timestamp":1454582514000},"page":"396-403","source":"Crossref","is-referenced-by-count":11,"title":["Presymptomatic MPTP<\/scp> Mice Show Neurotrophic S100B\/mRAGE<\/scp> Striatal Levels"],"prefix":"10.1111","volume":"22","author":[{"given":"Sofia D.","family":"Viana","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology and Experimental Therapeutics\/IBILI Faculty of Medicine University of Coimbra Coimbra Portugal"},{"name":"CNC.IBILI \u2013 University of Coimbra Coimbra Portugal"},{"name":"Instituto Polit\u00e9cnico de Coimbra ESTESC\u2010Coimbra Health School Farm\u00e1cia Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa C.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Experimental Therapeutics\/IBILI Faculty of Medicine University of Coimbra Coimbra Portugal"},{"name":"CNC.IBILI \u2013 University of Coimbra Coimbra Portugal"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula M.","family":"Canas","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology and Experimental 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