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Neuronal hyperactivity in a LRRK2-G2019S cellular model of Parkinson’s Disease

Edinson Lucumi Moreno, Siham Hachi, Sarah L. Nickels, Khalid I.W. Kane, Masha Moein, View ORCID ProfileJens C. Schwamborn, View ORCID ProfileAlexander Skupin, View ORCID ProfilePieter Vanden Berghe, View ORCID ProfileRonan M.T. Fleming
doi: https://doi.org/10.1101/2021.06.23.449591
Edinson Lucumi Moreno
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
2Department of Neurology, Brigham and Women’s Hospital, Harvard Medical School, Harvard University, 75 Francis St, Boston, USA
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Siham Hachi
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
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Sarah L. Nickels
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
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Khalid I.W. Kane
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
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Masha Moein
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
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Jens C. Schwamborn
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
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Alexander Skupin
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
3Department of Neuroscience, University of California, 9500 Gillman Dr, La Jolla, CA, USA
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Pieter Vanden Berghe
4Laboratory for Enteric Neuroscience, Translational Research in Gastrointestinal Disorders, ChroMetA Department, University of Leuven, Leuven Herestraat 49 3000, Leuven, Belgium
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Ronan M.T. Fleming
1Luxembourg Centre for Systems Biomedicine, University of Luxembourg, 6 avenue du Swing, L-4367 Belvaux, Luxembourg
5Division of Systems Biomedicine and Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Leiden, The Netherlands
6School of Medicine, National University of Ireland, Galway, University Rd, Galway, Ireland
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  • For correspondence: ronan.mt.fleming@gmail.com
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Abstract

Monogenic Parkinson’s Disease can be caused by a mutation in the leucine-rich repeat kinase 2 (LRRK2) gene, causing a late-onset autosomal dominant inherited form of Parkinson’s Disease. The function of the LRRK2 gene is incompletely understood, but several in vitro studies have reported that LRRK2-G2019S mutations affect neurite branching, calcium homeostasis and mitochondrial function, but thus far, there have been no reports of effects on electrophysiological activity. We assessed the neuronal activity of induced pluripotent stem cell derived neurons from Parkinson’s Disease patients with LRRK2-G2019S mutations and isogenic controls. Neuronal activity of spontaneously firing neuronal populations was recorded with a fluorescent calcium-sensitive dye (Fluo-4) and analysed with a novel image analysis pipeline that combined semi-automated neuronal segmentation and quantification of calcium transient properties. Compared with controls, LRRK2-G2019S mutants have shortened inter-spike intervals and an increased rate of spontaneous calcium transient induction.

Competing Interest Statement

The authors have declared no competing interest.

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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.
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Posted June 23, 2021.
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Neuronal hyperactivity in a LRRK2-G2019S cellular model of Parkinson’s Disease
Edinson Lucumi Moreno, Siham Hachi, Sarah L. Nickels, Khalid I.W. Kane, Masha Moein, Jens C. Schwamborn, Alexander Skupin, Pieter Vanden Berghe, Ronan M.T. Fleming
bioRxiv 2021.06.23.449591; doi: https://doi.org/10.1101/2021.06.23.449591
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Neuronal hyperactivity in a LRRK2-G2019S cellular model of Parkinson’s Disease
Edinson Lucumi Moreno, Siham Hachi, Sarah L. Nickels, Khalid I.W. Kane, Masha Moein, Jens C. Schwamborn, Alexander Skupin, Pieter Vanden Berghe, Ronan M.T. Fleming
bioRxiv 2021.06.23.449591; doi: https://doi.org/10.1101/2021.06.23.449591

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