Department of Neurosurgery, Air Force Medical Center of the Chinese PLA, Beijing, 100142, China.
Department of Anesthesiology, 7th Medical Center of the Chinese PLA General Hospital, Beijing, 100700, China.
Brain Res Bull. 2020 Dec;165:178-184. doi: 10.1016/j.brainresbull.2020.10.013. Epub 2020 Oct 16.
The translocator protein (TSPO), once known as peripheral-type benzodiazepine receptor, was reported to be related with several physiological functions. Etifoxine is a clinically available anxiolytic drug, and has recently shown neuroprotective effects as a TSPO ligand. The aim of the present study was to investigate the influence of etifoxine on LPS-induced neuroinflammation and cognitive dysfunction. C57/BL6 male mice were injected with etifoxine (50 mg/kg, i.p.) three days before lipopolysaccharide (LPS, 500 μg/kg, i.p.) administration. Etifoxine pretreatment alleviated hippocampal inflammation, increased brain levels of progesterone, allopregnanolone and attenuated cognitive dysfunction in LPS-injected mice. While LPS increased expression of caspase-3 and decreased p-Akt/Akt, etifoxine returned caspase-3 and p-Akt/Akt to control levels. Finasteride, a 5α-reductase inhibitor that blocked allopregnanolone production, partially reversed the effects of etifoxine. We concluded that etifoxine exerted neuroprotective effects in LPS-induced neuroinflammation and the neuroprotection may be related with increase of neurosteroids synthesis and decrease of apoptosis.
转位蛋白（TSPO），以前称为外周型苯二氮䓬受体，据报道与多种生理功能有关。依托非西定是一种临床可用的抗焦虑药物，最近作为 TSPO 配体显示出神经保护作用。本研究旨在探讨依托非西定对 LPS 诱导的神经炎症和认知功能障碍的影响。C57/BL6 雄性小鼠在脂多糖（LPS，500μg/kg，腹腔注射）给药前三天腹腔注射依托非西定（50mg/kg）。依托非西定预处理减轻了海马炎症，增加了大脑中孕酮、别孕烯醇酮的水平，并减轻了 LPS 注射小鼠的认知功能障碍。虽然 LPS 增加了 caspase-3 的表达，降低了 p-Akt/Akt，但依托非西定将 caspase-3 和 p-Akt/Akt 恢复到对照水平。非那雄胺，一种 5α-还原酶抑制剂，可阻止别孕烯醇酮的产生，部分逆转了依托非西定的作用。我们得出结论，依托非西定在 LPS 诱导的神经炎症中发挥了神经保护作用，这种神经保护作用可能与神经甾体合成的增加和凋亡的减少有关。
