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Aptamers: a new tool to understand the role of Pyruvate Dehydrogenase (PDC) in the pathophysiological mechanisms of Parkinson’s Disease in a rodent model


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


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 single strand), specifically designed to target the PDC, to reproduce a deficit in its activity in normal rats and analyze the behavioral and metabolic consequences.


This project will combine cerebral infusion of aptamers in rat by stereotaxic surgery, metabolomics analysis on blood and brain samples, behavioral evaluation of motor and neuropsychiatric state of the animals and immunohistochemistry.


  • 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.


S. Boulet
Email :
Tél : 04 56 52 06 70


Mise à jour le 26 juin 2020


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