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VGLUT modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration

View ORCID ProfileSilas A. Buck, View ORCID ProfileThomas Steinkellner, View ORCID ProfileDespoina Aslanoglou, Michael Villeneuve, Sai H. Bhatte, Victoria C. Childers, Sophie A. Rubin, Briana R. De Miranda, View ORCID ProfileEmma I. O’Leary, Elizabeth G. Neureiter, Keri J. Fogle, Michael J. Palladino, Ryan W. Logan, View ORCID ProfileJill R. Glausier, View ORCID ProfileKenneth N. Fish, David A. Lewis, View ORCID ProfileJ. Timothy Greenamyre, Antonello Bonci, View ORCID ProfileBrian D. McCabe, View ORCID ProfileClaire E. J. Cheetham, View ORCID ProfileThomas S. Hnasko, View ORCID ProfileZachary Freyberg
doi: https://doi.org/10.1101/2020.11.11.379008
Silas A. Buck
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Thomas Steinkellner
3Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
4Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Austria
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Despoina Aslanoglou
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Michael Villeneuve
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Sai H. Bhatte
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Victoria C. Childers
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Sophie A. Rubin
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Briana R. De Miranda
5Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
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Emma I. O’Leary
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
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Elizabeth G. Neureiter
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Keri J. Fogle
6Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA
7Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA
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Michael J. Palladino
6Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA
7Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA
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Ryan W. Logan
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Jill R. Glausier
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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Kenneth N. Fish
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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David A. Lewis
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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J. Timothy Greenamyre
5Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
7Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA
8Geriatric Research, Education and Clinical Center, VA Pittsburgh Healthcare System, Pittsburgh, PA, USA
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Antonello Bonci
9Work performed at the NIDA Intramural Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
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Brian D. McCabe
10Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
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Claire E. J. Cheetham
11Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
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Thomas S. Hnasko
3Department of Neurosciences, University of California, San Diego, La Jolla, CA, USA
12Research Service, VA San Diego Healthcare System, San Diego, CA, USA
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Zachary Freyberg
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
13Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA
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  • For correspondence: freyberg@pitt.edu
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Abstract

Age is the greatest risk factor for Parkinson’s disease (PD) which causes progressive loss of dopamine (DA) neurons, with males at greater risk than females. We found that vesicular glutamate transporter (VGLUT) expression mediates vulnerability to age-related DA neurodegeneration in a sex-dependent manner, providing a new mechanism for sex differences in selective DA neuron vulnerability. These findings lay the groundwork for novel therapeutic strategies to boost neuronal resilience throughout aging.

Competing Interest Statement

The authors have declared no competing interest.

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VGLUT modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration
Silas A. Buck, Thomas Steinkellner, Despoina Aslanoglou, Michael Villeneuve, Sai H. Bhatte, Victoria C. Childers, Sophie A. Rubin, Briana R. De Miranda, Emma I. O’Leary, Elizabeth G. Neureiter, Keri J. Fogle, Michael J. Palladino, Ryan W. Logan, Jill R. Glausier, Kenneth N. Fish, David A. Lewis, J. Timothy Greenamyre, Antonello Bonci, Brian D. McCabe, Claire E. J. Cheetham, Thomas S. Hnasko, Zachary Freyberg
bioRxiv 2020.11.11.379008; doi: https://doi.org/10.1101/2020.11.11.379008
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VGLUT modulates sex differences in dopamine neuron vulnerability to age-related neurodegeneration
Silas A. Buck, Thomas Steinkellner, Despoina Aslanoglou, Michael Villeneuve, Sai H. Bhatte, Victoria C. Childers, Sophie A. Rubin, Briana R. De Miranda, Emma I. O’Leary, Elizabeth G. Neureiter, Keri J. Fogle, Michael J. Palladino, Ryan W. Logan, Jill R. Glausier, Kenneth N. Fish, David A. Lewis, J. Timothy Greenamyre, Antonello Bonci, Brian D. McCabe, Claire E. J. Cheetham, Thomas S. Hnasko, Zachary Freyberg
bioRxiv 2020.11.11.379008; doi: https://doi.org/10.1101/2020.11.11.379008

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