THESE BENOIT GIRARD

Thèse
imgthese
Date: 2018-09-10 14:00

Lieu: Genopolys - Montpellier  |  Ville: Montpellier, France

IMPACT DE L’ACTIVATION DU RÉCEPTEUR MGLU7 DANS L’ÉPILEPSIE / IMPACT OF MGLU7 RECEPTOR ACTIVATION IN EPILEPSY

Benoît GIRARD

Epilepsy affects millions of patients worldwide. The available treatments are symptomatic, they treat seizures without preventing the progression of the disease and have heavy side effects. The discovery of new therapeutic targets and new compounds is therefore essential to overcome the limitations of current therapeutic strategies. Previous studies have demonstrated substantial involvement of the mGlu7 receptor in modulating not only excitability but also hypersynchronization of neural networks, two crucial factors affecting epileptic seizures. These discoveries were at the origin of a first publication that I completed at the beginning of my thesis (Tassin, Girard et al., 2016). Using a new mGlu7 receptor agonist, LSP2-9166, in my thesis I then studied the impact of this receptor in different epilepsy models in mice. Two complementary models were used: kindling, a chemical model induced by pentylenetetrazol (PTZ) which sensitizes the brain to induce generalized tonic-clonic seizures, and intra-hippocampal injection of kainate, mimicking mesial temporal lobe epilepsy in humans. At first, I observed an attenuation of the progression of the seizures severity in the PTZ kindling model, under the activation of the mGlu7 receptor. This effect was correlated with weaker inflammation, and microglial and astrocytic activation. In the intra-hippocampal injection model of KA, considered as drug-resistant, activation of the mGlu7 receptor during the epileptogenesis period increased the duration of interictal periods and decreased the duration of seizures as well as neuronal reorganization. Once chronic seizures were established, acute activation of the mGlu7 receptor decreased the number of seizures as strongly as diazepam, commonly used in clinical settings. Finally, chronic injections of LSP2-9166 into naive (non epileptic) animals do not generate any detectable cognitive or behavioral deficits or changes in mGlu7 receptor mRNA level. The activation of the mGlu7 receptor thus presents a strategic target in our two models. This work provides a better understanding of the role of the mGlu7 receptor in epileptogenesis. It participates in the search for future more adequate treatments.

Jury : Valérie Crépel, InMed Marseille Massimo Mantegazza, IMCP Sophia Antipolis Francine Acher, Université Paris Descartes Michel Vignes, IBMM Montpellier Antoine Depaulis, GIN Grenoble

 

 

Email
Adresse
141 Rue de la Cardonille
34090 Montpellier, France

 

Carte


 

Toutes les dates


  • 2018-09-10 14:00

Propulsé par iCagenda

 

Évènements

Lun Mar Mer Jeu Ven Sam Dim
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31