Laura Foucault-Fruchard's PhD Defense


on the May 30, 2018

Faculty of Medicine
Salle des Actes

Evaluation of the potential anti-inflammatory and neuroprotective effects of an α7 nAChR agonist in an in vivo rat model of neuroinflammation


Neuroinflammation is a key component of the pathophysiology of neurodegenerative diseases. This inflammatory process, characterized by the chronic activation of microglial cells, leads to neurodegeneration. To date, the management of patients with neurodegenerative diseases is based on symptomatic treatments. In recent years, the scientific community has focused its research on the regulation of the neuroinflammation. Today, regulating neuroinflammation with the aim of limiting neuronal death represents a major societal challenge in the management of patients affected by neurodegenerative diseases. In this thesis, we evaluated the potential anti-inflammatory and neuroprotective effects induced by an alpha 7 nicotinic acetylcholine receptor agonist (α7 nAChR), PHA 543613, in an in vivo rat neuroinflammatory model, induced by intrastriatal injection of quinolinic acid, an agonist of N-methyl-D-aspartate (NMDA) receptors. These investigations demonstrated the dose-dependent effect of PHA 543613 on the expression of the 18 kDa translocator protein (TSPO) which is a relevant marker of microglial activation. Concurrently, we evaluated neuronal survival and microglial activation. These experiments confirm our initial hypothesis: α7 nAChR agonists can improve neuron survival through potential modulation of microglial activation. These observations led us to continue our investigations through a mechanistic approach, and more precisely, to quantify the expression of a phase II antioxidant enzyme. Our results indicate that, by analogy with the peripheral anti-inflammatory cholinergic pathway, the activation of α7 nAChR localised on glial cells leads to the overexpression of heme oxygenase 1.


Neurodegenerative diseases, neuroinflammation, neurodegeneration, nicotinic acetylcholine receptors alpha 7, anti-inflammatory pathway.

Contact :
Dr. Sylvie Chalon :