Figure 6. Overexpression of Srd5a1 and Srd5a2 improved behavioral outcomes following CUS.

(A) (above) Schematic of lentiviral construct and targeting for overexpression of Srd5a1 and Srd5a2 in the BLA and the experimental timeline (below). (B) Representative immunofluorescence of GFP-tagged lentiviral targeting in the BLA of LV 5α1/2 mice. (C) The average mRNA expression of Srd5a1 and Srd5a2 increased in LV 5α1/2 mice compared to controls measured using qRT-PCR in the BLA of LV 5α1/2 mice, which were normalized to β-actin levels, control n=7, LV 5α1/2 n=4. (D) Overexpression of 5α1/2 decreased avoidance behaviors in CUS mice, exhibited as no change in the time spent in the center of the open field test compared to controls with no change in the total number of basic movements. control n=11, CUS+LV 5α1/2 n=8. These mice did not differ from controls in the time spent in the light zone or the number of basic movements performed in the light/dark box test control (E) n=11, CUS+LV 5α1/2 n=8. (F) CUS mice with overexpression of 5α1/2 in the BLA also demonstrated a decrease in stress-induced anxiety, indicated by an increase in the total time spent in the open arm of the elevated plus maze with no change in basic movements compared to controls. LV Srd5a1/2 mice subjected to CUS also exhibited a trend towards traveling further and performing more entries into the open arm of the elevated plus maze. control n=7, CUS+LV 5α1/2 n=8. (G) CUS mice with overexpression of 5α1/2 in the BLA exhibited a decrease in stress-induced helplessness as demonstrated by similar latency to immobility and overall time immobile in the tail suspension test. control n=8, CUS+LV 5α1/2 n=8. (H) summary of behavioral outcomes for CUS mice with lentiviral overexpression of 5α1/2 in the BLA. p > 0.05 is not significant, * Denotes p < 0.05, **p<0.01, ***p<0.001 using an unpaired t-test.