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Séminaire impromptu – Joshua Goldberg

10 février 2020 / 11:30 - 12:30

Lieu : Centre Broca nouvelle-Aquitaine

A neuroprotective response to a-synuclein causes dysautonomia in models of prodromal Parkinson’s disease

Joshua A. Goldberg,
Department of Medical Neurobiology, Institute of Medical Research Israel – Canada,
The Faculty of Medicine, The Hebrew University of Jerusalem, 9112102 Jerusalem, Israel


No disease-modifying therapy is currently available for Parkinson’s disease (PD), the second most common neurodegenerative disease. The long non-motor prodromal phase of PD is a window of opportunity for early detection and intervention. By developing a mutant a-synuclein selective overexpression mouse model of prodromal PD, we identified a cell-autonomous shrinkage of dorsal motor nucleus of the vagus (DMV) cholinergic neurons. In response to the shrinkage, DMV neurons successfully downregulate the surface expression of Cav channels to normalize calcium current density, but fail to downregulate Kv4 channel density. This functional remodeling of DMV neurons has two clinically-relevant implications: first, the elevated Kv4 current density impairs pacemaker function in vitro and in vivo, which in turn reduces gastrointestinal motility and alters cardiac function; second, the downregulation of Cav currents reduces basal oxidant stress in these neurons in transgenic mice that overexpress a-synuclein, which may explain why they are more resilient than other neurons vulnerable to a-synucleinopathy in PD. These findings can facilitate the rational design of physiological biomarkers to identify people at risk for PD.

Invité par François Georges – IMN

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Date :
10 février 2020
Heure :
11:30 - 12:30
Catégories d’Évènement:
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