α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability

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Standard

α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability. / Dagra, Abeer; Miller, Douglas R.; Lin, Min; Gopinath, Adithya; Shaerzadeh, Fatemeh; Harris, Sharonda; Sorrentino, Zachary A.; Stoier, Jonatan Fullerton; Velasco, Sophia; Azar, Janelle; Alonge, Adetola R.; Lebowitz, Joseph J.; Ulm, Brittany; Bu, Mengfei; Hansen, Carissa A.; Urs, Nikhil; Giasson, Benoit; Khoshbouei, Habibeh.

I: npj Parkinson's Disease, Bind 7, Nr. 1, 76, 2021.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

Harvard

Dagra, A, Miller, DR, Lin, M, Gopinath, A, Shaerzadeh, F, Harris, S, Sorrentino, ZA, Stoier, JF, Velasco, S, Azar, J, Alonge, AR, Lebowitz, JJ, Ulm, B, Bu, M, Hansen, CA, Urs, N, Giasson, B & Khoshbouei, H 2021, 'α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability', npj Parkinson's Disease, bind 7, nr. 1, 76. https://doi.org/10.1038/s41531-021-00210-w

APA

Dagra, A., Miller, D. R., Lin, M., Gopinath, A., Shaerzadeh, F., Harris, S., Sorrentino, Z. A., Stoier, J. F., Velasco, S., Azar, J., Alonge, A. R., Lebowitz, J. J., Ulm, B., Bu, M., Hansen, C. A., Urs, N., Giasson, B., & Khoshbouei, H. (2021). α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability. npj Parkinson's Disease, 7(1), [76]. https://doi.org/10.1038/s41531-021-00210-w

Vancouver

Dagra A, Miller DR, Lin M, Gopinath A, Shaerzadeh F, Harris S o.a. α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability. npj Parkinson's Disease. 2021;7(1). 76. https://doi.org/10.1038/s41531-021-00210-w

Author

Dagra, Abeer ; Miller, Douglas R. ; Lin, Min ; Gopinath, Adithya ; Shaerzadeh, Fatemeh ; Harris, Sharonda ; Sorrentino, Zachary A. ; Stoier, Jonatan Fullerton ; Velasco, Sophia ; Azar, Janelle ; Alonge, Adetola R. ; Lebowitz, Joseph J. ; Ulm, Brittany ; Bu, Mengfei ; Hansen, Carissa A. ; Urs, Nikhil ; Giasson, Benoit ; Khoshbouei, Habibeh. / α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability. I: npj Parkinson's Disease. 2021 ; Bind 7, Nr. 1.

Bibtex

@article{5f93a843932b436ca03a39dd94f917bc,
title = "α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability",
abstract = "Pathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease. The presence of aberrant intracellular pathological inclusions of the protein alpha-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson's disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive alpha-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of alpha-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by alpha-synuclein overexpression. These studies demonstrate that alpha-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson's disease progression with significant therapeutic implications.",
keywords = "TYROSINE-HYDROXYLASE PHOSPHORYLATION, SUBSTANTIA-NIGRA, IN-VIVO, PARKINSONS-DISEASE, MESSENGER-RNA, FIRING RATE, RECEPTOR AGONIST, D2 RECEPTORS, HUMAN BRAIN, CELL-LINE",
author = "Abeer Dagra and Miller, {Douglas R.} and Min Lin and Adithya Gopinath and Fatemeh Shaerzadeh and Sharonda Harris and Sorrentino, {Zachary A.} and Stoier, {Jonatan Fullerton} and Sophia Velasco and Janelle Azar and Alonge, {Adetola R.} and Lebowitz, {Joseph J.} and Brittany Ulm and Mengfei Bu and Hansen, {Carissa A.} and Nikhil Urs and Benoit Giasson and Habibeh Khoshbouei",
year = "2021",
doi = "10.1038/s41531-021-00210-w",
language = "English",
volume = "7",
journal = "npj Parkinson's Disease",
issn = "2373-8057",
publisher = "Springer",
number = "1",

}

RIS

TY - JOUR

T1 - α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability

AU - Dagra, Abeer

AU - Miller, Douglas R.

AU - Lin, Min

AU - Gopinath, Adithya

AU - Shaerzadeh, Fatemeh

AU - Harris, Sharonda

AU - Sorrentino, Zachary A.

AU - Stoier, Jonatan Fullerton

AU - Velasco, Sophia

AU - Azar, Janelle

AU - Alonge, Adetola R.

AU - Lebowitz, Joseph J.

AU - Ulm, Brittany

AU - Bu, Mengfei

AU - Hansen, Carissa A.

AU - Urs, Nikhil

AU - Giasson, Benoit

AU - Khoshbouei, Habibeh

PY - 2021

Y1 - 2021

N2 - Pathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease. The presence of aberrant intracellular pathological inclusions of the protein alpha-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson's disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive alpha-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of alpha-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by alpha-synuclein overexpression. These studies demonstrate that alpha-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson's disease progression with significant therapeutic implications.

AB - Pathophysiological damages and loss of function of dopamine neurons precede their demise and contribute to the early phases of Parkinson's disease. The presence of aberrant intracellular pathological inclusions of the protein alpha-synuclein within ventral midbrain dopaminergic neurons is one of the cardinal features of Parkinson's disease. We employed molecular biology, electrophysiology, and live-cell imaging to investigate how excessive alpha-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of alpha-synuclein in mouse (male and female) dopaminergic neurons altered neuronal firing properties, calcium dynamics, dopamine release, protein expression, and morphology. Moreover, prolonged exposure to the D2 receptor agonist, quinpirole, rescues many of the alterations induced by alpha-synuclein overexpression. These studies demonstrate that alpha-synuclein dysregulation of neuronal activity contributes to the vulnerability of dopaminergic neurons and that modulation of D2 receptor activity can ameliorate the pathophysiology. These findings provide mechanistic insights into the insidious changes in dopaminergic neuronal activity and neuronal loss that characterize Parkinson's disease progression with significant therapeutic implications.

KW - TYROSINE-HYDROXYLASE PHOSPHORYLATION

KW - SUBSTANTIA-NIGRA

KW - IN-VIVO

KW - PARKINSONS-DISEASE

KW - MESSENGER-RNA

KW - FIRING RATE

KW - RECEPTOR AGONIST

KW - D2 RECEPTORS

KW - HUMAN BRAIN

KW - CELL-LINE

U2 - 10.1038/s41531-021-00210-w

DO - 10.1038/s41531-021-00210-w

M3 - Journal article

C2 - 34408150

VL - 7

JO - npj Parkinson's Disease

JF - npj Parkinson's Disease

SN - 2373-8057

IS - 1

M1 - 76

ER -

ID: 277188070