Aim: The aim of this study is to examine the effect of etifoxine on β-amyloid-induced toxicity
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.