Contenu

x

Moteur de recherche interne

Grenoble Institut des Neurosciences Grenoble Institut des Neurosciences

  • Youtube
  • Linkedin
  • Twitter

Accueil > Nous rejoindre > Offres de stages

Accéder au plan complet du site

Role of Pyruvate Dehydrogenase (PDC) in the pathophysiological mechanisms of Parkinson’s Disease: use of aptamers or viral vectors in a rodent model

Objectifs

Understand the implication of the Pyruvate Dehydrogenase Complex (PDC) in the different phases of Parkinson’s disease (PD) thanks to the selective modulation of its expression in vivo with aptamers or viral vectors.

Résumé

PD is a well known neurodegenerative disorder. Unfortunately, its diagnosis, which relies on the expression of motor symptoms appearing when most of the dopaminergic neurons of the substantia nigra pars compacta are lost, is too late to allow the development of curative treatments that remain symptomatic. Thus, detect the disease earlier represent the key step to solve this therapeutic issue. Yet, beyond the motor symptoms, PD is also associated with a plethora of neuropsychiatric symptoms, which appear early in the disease, before the motor symptoms. By using H1NMR based metabolomics analysis on serum and brain samples of a specific model of the different phases of PD in the rat, associated with behavioral analysis, our team has previously shown the existence of a specific metabolic profile associated with each phase of PD and especially the early phase. The discriminant metabolites of these profiles suggest that a decrease of activity in the Pyruvate Dehydrogenase Complex, a key enzyme of the energetic metabolism, could be involved in the pathophysiology of PD, as soon as the early phase. Thus, the objective of this M2 internship is to use aptamers (short DNA or RNA single strand) or viral vectors, specifically designed to target the PDC, to reproduce a deficit in its activity in normal rats and analyze the behavioral and metabolic consequences.

Méthodes

This project will combine cerebral infusion of viral vectors or aptamers in rat by stereotaxic surgery, behavioral evaluation of motor and neuropsychiatric state of the animals and immunohistochemistry.

Références

  • Magnard R*, Vachez Y*, Carcenac C, Krack P, David O, Savasta M, Boulet S*, Carnicella S* (2016) What can rodent models tell us about apathy and associated neuropsychiatric symptoms in Parkinson's disease? Transl Psychiatry 6:e753
  • Favier M, Duran T, Drui G, Carcenac C, Savasta M, Carnicella S (2014) Full reversion of motivational deficits by pramipexole in a rodent model of Parkinson’s disease. Mov Disord 7:912-20
  • Drui G*, Carnicella S*, Carcenac C, Favier M, Bertrand A, Boulet S, Savasta M (2014) Loss of dopaminergic nigrostriatal neurons accounts for the motivational and affective deficits in Parkinson's disease. Molecular Psychiatry 19(3):358-67

Domaines d'expertise requis

Interest for integrated neurophysiology, animal behavior, cellular and molecular biology, immunohistochemistry

Contacts

S. Boulet
Email : sabrina.boulet@univ-grenoble-alpes.fr
Tél: 04 56 52 06 70

Mise à jour le 6 juin 2019

Contacts

Pour une candidature spontanée, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.

Pour les stages de licence et de 3ème, voir les modalités de demande spécifiques sur les pages correspondantes. 

Membres
Associés renforcés
Associés simples