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In this study, we aimed to examine the effects of MB in Parkinson's disease (PD) <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> models by using 1\u2010methyl\u20104\u2010phenyl\u20101,2,3,6\u2010tetrahydropyridine (MPTP)\/1\u2010methyl\u20104\u2010phenylpyridinium (MPP<jats:sup>+<\/jats:sup>) with a focus on possible effects on induction of neurotrophic factors. Our results indicate that pretreatment with MB significantly attenuated MPTP\u2010induced loss of dopaminergic neurons, glial cell activation, and depletion of dopamine. We also found that MB upregulated brain\u2010derived neurotrophic factor (BDNF) and activated its downstream signaling pathways, suggesting that BDNF might be a contributor to MB\u2010associated neuroprotection. Specific inhibition of the BDNF receptor or extracellular signal\u2010regulated kinase (Erk) reversed the MB\u2010mediated protection against MPP<jats:sup>+<\/jats:sup> toxicity, thus implying a role for BDNF and the Erk pathway in the neuroprotective effects. Taken together, our data suggest that MB protects neurons from MPTP neurotoxicity via induction of BDNF. Further study to determine whether MB preserves dopaminergic neurons in the brains of PD patients is warranted.<\/jats:p>","DOI":"10.1111\/nyas.13870","type":"journal-article","created":{"date-parts":[[2018,6,8]],"date-time":"2018-06-08T06:11:01Z","timestamp":1528438261000},"page":"58-71","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Methylene blue protects dopaminergic neurons against MPTP\u2010induced neurotoxicity by upregulating brain\u2010derived neurotrophic factor"],"prefix":"10.1111","volume":"1431","author":[{"given":"Sunil","family":"Bhurtel","sequence":"first","affiliation":[{"name":"College of Pharmacy Yeungnam University  Gyeongsan Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikita","family":"Katila","sequence":"additional","affiliation":[{"name":"College of Pharmacy Yeungnam University  Gyeongsan Republic of 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