Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration [preprint]
dc.contributor.author | Buck, Silas A | |
dc.contributor.author | Rubin, Sophie A | |
dc.contributor.author | Kunkhyen, Tenzin | |
dc.contributor.author | Treiber, Christoph D | |
dc.contributor.author | Xue, Xiangning | |
dc.contributor.author | Fenno, Lief E | |
dc.contributor.author | Mabry, Samuel J | |
dc.contributor.author | Sundar, Varun R | |
dc.contributor.author | Yang, Zilu | |
dc.contributor.author | Shah, Divia | |
dc.contributor.author | Ketchesin, Kyle D | |
dc.contributor.author | Becker-Krail, Darius D | |
dc.contributor.author | Vasylieva, Iaroslavna | |
dc.contributor.author | Smith, Megan C | |
dc.contributor.author | Weisel, Florian J | |
dc.contributor.author | Wang, Wenjia | |
dc.contributor.author | Erickson-Oberg, M Quincy | |
dc.contributor.author | O'Leary, Emma I | |
dc.contributor.author | Aravind, Eshan | |
dc.contributor.author | Ramakrishnan, Charu | |
dc.contributor.author | Kim, Yoon Seok | |
dc.contributor.author | Wu, Yanying | |
dc.contributor.author | Quick, Matthias | |
dc.contributor.author | Coleman, Jonathan A | |
dc.contributor.author | MacDonald, William A | |
dc.contributor.author | Elbakri, Rania | |
dc.contributor.author | De Miranda, Briana R | |
dc.contributor.author | Palladino, Michael J | |
dc.contributor.author | McCabe, Brian D | |
dc.contributor.author | Fish, Kenneth N | |
dc.contributor.author | Seney, Marianne L | |
dc.contributor.author | Rayport, Stephen | |
dc.contributor.author | Mingote, Susana | |
dc.contributor.author | Deisseroth, Karl | |
dc.contributor.author | Hnasko, Thomas S | |
dc.contributor.author | Awatramani, Rajeshwar | |
dc.contributor.author | Watson, Alan M | |
dc.contributor.author | Waddell, Scott | |
dc.contributor.author | Cheetham, Claire E J | |
dc.contributor.author | Logan, Ryan W | |
dc.contributor.author | Freyberg, Zachary | |
dc.date.accessioned | 2023-11-29T15:25:49Z | |
dc.date.available | 2023-11-29T15:25:49Z | |
dc.date.issued | 2023-10-03 | |
dc.identifier.citation | Buck 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.doi | 10.1101/2023.10.02.560584 | en_US |
dc.identifier.pmid | 37873436 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/52800 | |
dc.description | This article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review. | en_US |
dc.description.abstract | Parkinson'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.iso | en | en_US |
dc.relation.ispartof | bioRxiv | en_US |
dc.relation.url | https://doi.org/10.1101/2023.10.02.560584 | en_US |
dc.rights | 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 | en_US |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Drosophila | en_US |
dc.subject | Parkinson’s disease | en_US |
dc.subject | RNAseq | en_US |
dc.subject | VGLUT2 | en_US |
dc.subject | dVGLUT | en_US |
dc.subject | dopamine | en_US |
dc.subject | glutamate | en_US |
dc.subject | neurodegeneration | en_US |
dc.subject | paraquat | en_US |
dc.subject | Neuroscience | en_US |
dc.title | Sexually dimorphic mechanisms of VGLUT-mediated protection from dopaminergic neurodegeneration [preprint] | en_US |
dc.type | Preprint | en_US |
dc.source.journaltitle | bioRxiv : the preprint server for biology | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United Kingdom | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.source.country | United States | |
dc.identifier.journal | bioRxiv : the preprint server for biology | |
refterms.dateFOA | 2023-11-29T15:25:51Z | |
dc.contributor.department | Neurobiology | en_US |
dc.contributor.department | Psychiatry | en_US |