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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
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
Despoina Aslanoglou
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Michael Villeneuve
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Sai H. Bhatte
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Victoria C. Childers
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Sophie A. Rubin
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Briana R. De Miranda
5Department of Neurology, University of Pittsburgh, Pittsburgh, PA, USA
Emma I. O’Leary
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
Elizabeth G. Neureiter
1Center for Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Keri J. Fogle
6Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA
7Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA
Michael J. Palladino
6Department of Pharmacology & Chemical Biology, University of Pittsburgh, Pittsburgh, PA
7Pittsburgh Institute for Neurodegenerative Diseases, University of Pittsburgh, Pittsburgh, PA, USA
Ryan W. Logan
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Jill R. Glausier
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
Kenneth N. Fish
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
David A. Lewis
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
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
Antonello Bonci
9Work performed at the NIDA Intramural Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, USA
Brian D. McCabe
10Brain Mind Institute, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland
Claire E. J. Cheetham
11Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA, USA
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
Zachary Freyberg
2Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA
13Department of Cell Biology, University of Pittsburgh, Pittsburgh, PA, USA

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.
Copyright
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Posted November 12, 2020.
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
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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