α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability.
α-Synuclein-induced dysregulation of neuronal activity contributes to murine dopamine neuron vulnerability.
NPJ Parkinson's disease (2021-08-20)
Abeer Dagra, Douglas R Miller, Min Lin, Adithya Gopinath, Fatemeh Shaerzadeh, Sharonda Harris, Zachary A Sorrentino, Jonatan Fullerton Støier, Sophia Velasco, Janelle Azar, Adetola R Alonge, Joseph J Lebowitz, Brittany Ulm, Mengfei Bu, Carissa A Hansen, Nikhil Urs, Benoit I Giasson, Habibeh Khoshbouei
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 α-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 α-synuclein expression alters multiple characteristics of dopaminergic neuronal dynamics and dopamine transmission in cultured dopamine neurons conditionally expressing GCaMP6f. We found that overexpression of α-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 α-synuclein overexpression. These studies demonstrate that α-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.
Terreno Eagle modificato di Dulbecco - alto glucosio, With 4500 mg/L glucose, sodium pyruvate, and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture
Protease Inhibitor Cocktail Set I, A cocktail of five protease inhibitors that will inhibit a broad range of proteases and esterases. Supplied with a data sheet.