Veronique Riban *, Johann Meunier , Dorothee Buttigieg, Vanessa Villard and Marc Verleye Pages 227 - 240 ( 14 )
Aim: The aim of this study is to examine the effect of etifoxine on β-amyloid-induced toxicity models.
Background: Etifoxine is an anxiolytic compound with a dual mechanism of action; it is a positive allosteric modulator of GABAergic receptors as well as a ligand for the 18 kDa mitochondrial Translocator Protein (TSPO). TSPO has recently raised interest in Alzheimer’s Disease (AD), and experimental studies have shown that some TSPO ligands could induce neuroprotective effects in animal models.
Objective: In this study, we examined the potential protective effect of etifoxine in an in vitro and an in vivo model of amyloid beta (Aβ)-induced toxicity in its oligomeric form, which is a crucial factor in AD pathologic mechanisms.
Methods: Neuronal cultures were intoxicated with Aβ1-42, and the effects of etifoxine on oxidative stress, Tau-hyperphosphorylation and synaptic loss were quantified. In a mice model, behavioral deficits induced by intracerebroventricular administration of Aβ25-35 were measured in a spatial memory test, the spontaneous alternation and in a contextual memory test, the passive avoidance test.
Results: In neuronal cultures intoxicated with Aβ1-42, etifoxine dose-dependently decreased oxidative stress (methionine sulfoxide positive neurons), tau-hyperphosphorylation and synaptic loss (ratio PSD95/synaptophysin). In a mice model, memory impairments were fully alleviated by etifoxine administered at anxiolytic doses (12.5-50mg/kg). In addition, markers of oxidative stress and apoptosis were decreased in the hippocampus of these animals.
Conclusion: Our results have shown that in these two models, etifoxine could fully prevent neurotoxicity and pathological changes induced by Aβ. These results confirm that TSPO ligands could offer an interesting therapeutic approach to Alzheimer’s disease.
Alzheimer's disease, etifoxine, mice model, in vitro models, Translocator Protein (TSPO), amyloid beta peptide.
Pharmacology Department, Biocodex, 3 Chemin d’Armancourt, 60200 Compiegne, Amylgen, 2196 Boulevard de la Lironde, 34980 Montferrier sur Lez, Neuron Experts SAS, 51 Bd Pierre Dramard, 13916 Marseille, Amylgen, 2196 Boulevard de la Lironde, 34980 Montferrier sur Lez, Pharmacology Department, Biocodex, 3 Chemin d’Armancourt, 60200 Compiegne