Overexpression Of 18kDa Translocator Protein In Mouse Hippocampal Dentate Gyrus Mediates Anxiolytic And Depressive Behavior

The 18 kDa translocator protein(TSPO),primarily located in glial cells and mediates the translocation of cholesterol from the outer to the inner mitochondrial membrane in the central nervous system,is the rate-limiting step in the synthesis of neurosteroids such as pregnenolone and progesterone.The level of neurosteroid,a potent positive allosteric modulator of the activity of γ-aminobutyric acid(GABA)receptors,glutamate receptors,and other neurotransmitters and their receptor function,was markedly altered in association with the development of stress anxiety and depression and Post-traumatic stress disorder.Recently the study found,TSPO would be a potential anxiolytic and antidepressant of psychiatric disorders the rapeutic target.To investigate the effects of hippocampal dentate gyrus lentivirus-TSPO microinfusion on anxiolytic and antidepressant-like behaviors in mice,which provided a experimental basis that TSPO could be a new potential therapuetic target for anxiolytic and antidepressant in the future.Specifically,this study used the lentiviral vectors mediating TPSO overexpression to assess the overexpression effects of in the hippocampal dentate gyrus in adult male ICR mice.Fluorescence inverted microscopy tracked the lentivirus-mediated transfection in vivo was traced by monitoring the high and specific overexpression of TSPO.Behavioral tests were carried out.Respectively,mice were examined anxiolytic-like behavior such as the elevated plus maze test,the staircase test,light dark box test for the 12,14 and 16 d and two behavioral despair models,the tail suspension test and the forced swimming test for the18 and 21 d.Western blot and ELISA was used to evaluate the effects of TSPO expression and the concentration of allopregnanolone in hippocampal tissues(3 mm in diameter around the injection site on both sides).To explore the relationship between TSPO and anxiety and depression in hippocampus dentate gyrus.The results of experiment showed that the level of TSPO expression in hippocampal tissues were significantly increased than theLV-control group for the 12 d after LV-TSPO microinjection(P=0.001).LV-control were expressed well in the dentate gyrus,as indicated by EGFP-positive cells(green).The open field test was carried out 12 days after LV-TSPO microinjection,and no significant alterations of crossings(p>0.05)and rearings(p>0.05);LV-TSPO significantly increased the time in the central area(P<0.05);LV-TSPO significantly increased the open arms entries percentage and open arms time percentage without changing total entries and total time in the elevated plus-maze test(P<0.05;P<0.01);LV-TSPO significantly decreased number of rearings without changing the number of steps in staircase test(P<0.05);LV-TSPO increased entries to light area and duration in light area in light-dark transition test(P<0.05;P<0.05).These results indicated that TSPO overexpression ameliorated the anxious behaviours.LV-TSPO significantly decreased immobility time in the tail suspension test and forced swimming test than the LV-control group(P<0.01;P<0.05).These results indicated that TSPO overexpression ameliorated the depression-related behaviours.At the same time,the level of TSPO expression in hippocampal tissues(3 mm in diameter around the injection site on both sides)were significantly increased and the concentration of allopregnanolone were significantly increased(P<0.05).The present results suggest that the overexpression of TSPO in mice hippocamus dentate gyrus could exert anxiolytic and antidepressant-like behavior in mice hippocamus dentate gyrus.Allopregnanolone in hippocampal dentate gyrusis contributes to the behavioral effects.