Publications

Dernière publication 27/01/2014

Progressive Parkinsonism by acute dysfunction of excitatory amino acid transport

Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra (SN) dopamine neurons, involving a multifactorial...

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    [title] => Progressive Parkinsonism by acute dysfunction of excitatory amino acid transport
    [paragraph] => Progressive Parkinsonism by acute dysfunction of excitatory amino acid transporters in the rat substantia nigra
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Authors
M. Assousa, L. Had-Aissounia, P. Gubellinia, C. Melona, I. Nafia et al.

 Lab
Aix-Marseille Université, Marseille, France
Journal
Neurobiology of Disease
Abstract
Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra (SN) dopamine neurons, involving a multifactorial cascade of pathogenic events. Here we explored the hypothesis that dysfunction of excitatory amino acid transporters (EAATs) might be involved. Acutely-induced dysfunction of EAATs in the rat SN, by single unilateral injection of their substrate inhibitor l-trans-pyrrolidine-2,4-dicarboxylate (PDC), triggers a neurodegenerative process mimicking several PD features. Dopamine neurons are selectively affected, consistent with their sustained excitation by PDC measured by slice electrophysiology. The anti-oxidant N-acetylcysteine and the NMDA receptor antagonists ifenprodil and memantine provide neuroprotection. Besides oxidative stress and NMDA receptor-mediated excitotoxicity, glutathione depletion and neuroinflammation characterize the primary insult. Most interestingly, the degeneration progresses overtime with unilateral to bilateral and caudo-rostral evolution. Transient adaptive changes in dopamine function markers in SN and striatum accompany cell loss and axonal dystrophy, respectively. Motor deficits appear when neuron loss exceeds 50% in the most affected SN and striatal dopamine tone is dramatically reduced. These findings outline a functional link between EAAT dysfunction and several PD pathogenic mechanisms/pathological hallmarks, and provide a novel acutely-triggered model of progressive Parkinsonism.
BIOSEB Instruments Used
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Une façon simple pour mesurer l'activité des rongeurs sur plusieurs jours dans leurs cages de vie. Basé uniquement sur l'analyse du poids de l'animal, L'ACTIVMETRE Bioseb permet une mesure précise de l'activité et des déplacements du rongeur (rat et souris), dans toutes les conditions d'éclairage.
fiber_new Possibilité d’ajouter la mesure de l’activité verticale des animaux dans la cage (en option).

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