TSPO ligand etifoxine attenuates LPS-induced cognitive dysfunction in mice

Area of Science:

• Neuroscience
• Pharmacology
• Immunology

Background:

• The translocator protein (TSPO) is implicated in various physiological functions.
• Etifoxine, an anxiolytic, demonstrates neuroprotective properties as a TSPO ligand.

Purpose of the Study:

• To investigate the effects of etifoxine on lipopolysaccharide (LPS)-induced neuroinflammation.
• To assess etifoxine's impact on cognitive dysfunction in an LPS-induced mouse model.

Main Methods:

• C57/BL6 male mice were pretreated with etifoxine before LPS administration.
• Evaluated hippocampal inflammation, brain neurosteroid levels (progesterone, allopregnanolone), and cognitive function.
• Assessed caspase-3 expression and Akt phosphorylation (p-Akt/Akt) levels.
• Utilized finasteride to investigate the role of allopregnanolone.

Main Results:

• Etifoxine pretreatment alleviated hippocampal inflammation and cognitive deficits in LPS-injected mice.
• Etifoxine increased brain levels of progesterone and allopregnanolone.
• Etifoxine normalized LPS-induced increases in caspase-3 and decreases in p-Akt/Akt.
• Finasteride partially reversed etifoxine's beneficial effects, indicating a role for allopregnanolone.

Conclusions:

• Etifoxine exerts significant neuroprotective effects against LPS-induced neuroinflammation and cognitive dysfunction.
• Neuroprotection by etifoxine is associated with increased neurosteroid synthesis and reduced apoptosis.
• These findings support etifoxine's potential as a therapeutic agent for neuroinflammatory conditions.