Research reportOver-expression of TSPO in the hippocampal CA1 area alleviates cognitive dysfunction caused by lipopolysaccharide in mice

- TSPO over-expression increased progesterone and allopregnanolone synthesis.
- TSPO over-expression in hippocampal CA1 mitigated LPS-induced cognitive dysfunction.
- Finasteride partially reversed the behavioral effects of TSPO over-expression.
- TSPO may be an attractive drug target for controlling neuroinflammation.

The translocator protein 18 kDa (TSPO) is closely related to regulation of immune/inflammatory response. However, the putative role and signaling mechanisms of TSPO in regulation of neuroinflammation remain unclear. GV287 lentiviral vectors mediating TSPO over-expression were injected into bilateral hippocampal CA1 areas to test whether TSPO over-expression was neuroprotective in lipopolysaccharide (LPS)-induced mice model. Finasteride, a blocker of allopregnanolone production, was used to test whether the protective effects were related to steroideogenesis. The results demonstrated that TSPO over-expression increased progesterone and allopregnanolone synthesis. TSPO over-expression in CA1 area improved LPS-induced cognitive deficiency in mice and this cognitive improvement was reversed by finasteride administration. These data suggest that up-regulation of TSPO level during neuroinflammation may be an adaptive response mechanism, a way to provide more neurosteroids. We confer that TSPO could be an attractive drug target for controlling neuroinflammation in the future.