Overexpression of the 18 kDa Translocator Protein (TSPO) in the Hippocampal Dentate Gyrus Produced Anxiolytic and Antidepressant-Like Behavioral Effects

The study demonstrated that overexpression of the 18 kDa translocator protein (TSPO) in the hippocampal dentate gyrus of mice led to significant anxiolytic and antidepressant-like behavioral effects. This was achieved through lentiviral transduction, which increased TSPO expression and subsequently elevated allopregnanolone synthesis in the hippocampus. The behavioral improvements were reversed by the TSPO antagonist PK11195 and the steroidogenic enzyme inhibitor finasteride, indicating that the effects were mediated by TSPO and its role in neurosteroid biosynthesis. These findings suggested that TSPO could be a potential therapeutic target for treating anxiety and depression.