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dc.contributor.authorBuck, Silas A
dc.contributor.authorRubin, Sophie A
dc.contributor.authorKunkhyen, Tenzin
dc.contributor.authorTreiber, Christoph D
dc.contributor.authorXue, Xiangning
dc.contributor.authorFenno, Lief E
dc.contributor.authorMabry, Samuel J
dc.contributor.authorSundar, Varun R
dc.contributor.authorYang, Zilu
dc.contributor.authorShah, Divia
dc.contributor.authorKetchesin, Kyle D
dc.contributor.authorBecker-Krail, Darius D
dc.contributor.authorVasylieva, Iaroslavna
dc.contributor.authorSmith, Megan C
dc.contributor.authorWeisel, Florian J
dc.contributor.authorWang, Wenjia
dc.contributor.authorErickson-Oberg, M Quincy
dc.contributor.authorO'Leary, Emma I
dc.contributor.authorAravind, Eshan
dc.contributor.authorRamakrishnan, Charu
dc.contributor.authorKim, Yoon Seok
dc.contributor.authorWu, Yanying
dc.contributor.authorQuick, Matthias
dc.contributor.authorColeman, Jonathan A
dc.contributor.authorMacDonald, William A
dc.contributor.authorElbakri, Rania
dc.contributor.authorDe Miranda, Briana R
dc.contributor.authorPalladino, Michael J
dc.contributor.authorMcCabe, Brian D
dc.contributor.authorFish, Kenneth N
dc.contributor.authorSeney, Marianne L
dc.contributor.authorRayport, Stephen
dc.contributor.authorMingote, Susana
dc.contributor.authorDeisseroth, Karl
dc.contributor.authorHnasko, Thomas S
dc.contributor.authorAwatramani, Rajeshwar
dc.contributor.authorWatson, Alan M
dc.contributor.authorWaddell, Scott
dc.contributor.authorCheetham, Claire E J
dc.contributor.authorLogan, Ryan W
dc.contributor.authorFreyberg, Zachary
dc.date.accessioned2023-11-29T15:25:49Z
dc.date.available2023-11-29T15:25:49Z
dc.date.issued2023-10-03
dc.identifier.citationBuck SA, Rubin SA, Kunkhyen T, Treiber CD, Xue X, Fenno LE, Mabry SJ, Sundar VR, Yang Z, Shah D, Ketchesin KD, Becker-Krail DD, Vasylieva I, Smith MC, Weisel FJ, Wang W, Erickson-Oberg MQ, O'Leary EI, Aravind E, Ramakrishnan C, Kim YS, Wu Y, Quick M, Coleman JA, MacDonald WA, Elbakri R, De Miranda BR, Palladino MJ, McCabe BD, Fish KN, Seney ML, Rayport S, Mingote S, Deisseroth K, Hnasko TS, Awatramani R, Watson AM, Waddell S, Cheetham CEJ, Logan RW, Freyberg Z. Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration. bioRxiv [Preprint]. 2023 Oct 3:2023.10.02.560584. doi: 10.1101/2023.10.02.560584. PMID: 37873436; PMCID: PMC10592912.en_US
dc.identifier.doi10.1101/2023.10.02.560584en_US
dc.identifier.pmid37873436
dc.identifier.urihttp://hdl.handle.net/20.500.14038/52800
dc.descriptionThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.en_US
dc.description.abstractParkinson's disease (PD) targets some dopamine (DA) neurons more than others. Sex differences offer insights, with females more protected from DA neurodegeneration. The mammalian vesicular glutamate transporter VGLUT2 and Drosophila ortholog dVGLUT have been implicated as modulators of DA neuron resilience. However, the mechanisms by which VGLUT2/dVGLUT protects DA neurons remain unknown. We discovered DA neuron dVGLUT knockdown increased mitochondrial reactive oxygen species in a sexually dimorphic manner in response to depolarization or paraquat-induced stress, males being especially affected. DA neuron dVGLUT also reduced ATP biosynthetic burden during depolarization. RNA sequencing of VGLUT+ DA neurons in mice and flies identified candidate genes that we functionally screened to further dissect VGLUT-mediated DA neuron resilience across PD models. We discovered transcription factors modulating dVGLUT-dependent DA neuroprotection and identified dj-1β as a regulator of sex-specific DA neuron dVGLUT expression. Overall, VGLUT protects DA neurons from PD-associated degeneration by maintaining mitochondrial health.en_US
dc.language.isoenen_US
dc.relation.ispartofbioRxiven_US
dc.relation.urlhttps://doi.org/10.1101/2023.10.02.560584en_US
dc.rightsThe copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectDrosophilaen_US
dc.subjectParkinson’s diseaseen_US
dc.subjectRNAseqen_US
dc.subjectVGLUT2en_US
dc.subjectdVGLUTen_US
dc.subjectdopamineen_US
dc.subjectglutamateen_US
dc.subjectneurodegenerationen_US
dc.subjectparaquaten_US
dc.subjectNeuroscienceen_US
dc.titleSexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration [preprint]en_US
dc.typePreprinten_US
dc.source.journaltitlebioRxiv : the preprint server for biology
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited Kingdom
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.source.countryUnited States
dc.identifier.journalbioRxiv : the preprint server for biology
refterms.dateFOA2023-11-29T15:25:51Z
dc.contributor.departmentNeurobiologyen_US
dc.contributor.departmentPsychiatryen_US


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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.; Attribution-NonCommercial-NoDerivatives 4.0 International