(A) Neuronal cells were transfected with BDNF, HSJ1a, HSJ1b, or the corresponding empty vectors. Forty-eight hours after transfection, cells were washed with PBS and incubated for 30 minutes with DMEM, and supernatants (super.) were collected. Data (ANOVA, F _2,31 = 9.17; P = 0.0007) revealed that HSJ1b (post-hoc Fisher’s test, P = 0.0002), but not HSJ1a (NS), induced a statistically significant increase in BDNF release. (B) Data (ANOVA, F _3,39 = 323.66; P < 0.0001) revealed a statistically significant increase in BDNF content in the supernatant of 100 μM cystamine-treated cells at 24, 48, and 72 hours (post-hoc Fisher’s test, P < 0.0001). (C) Cells transfected with BDNF and treated with cystamine were analyzed by immunoblotting with anti-BDNF and anti–β-actin antibodies. (D) Data (ANOVA, F _3,29 = 26.01; P < 0.0001) revealed a statistically significant decrease in HSJ1 transcripts in cells transfected with siRNA-HSJ1 compared with control cells with or without cystamine treatment (post-hoc Fisher’s test, P < 0.0001). Cystamine increased HSJ1 transcripts in control conditions (post-hoc Fisher’s test, P = 0.002) but not in the presence of siRNA-HSJ1 (NS). (E) Cystamine did not increase BDNF release when HSJ1b levels were lowered by RNAi-HSJ1 (ANOVA, F _3,19 = 7.59; P = 0.0016). Cells were cotransfected with BDNF and pSUPER-RNAi-HSJ1 and treated with cystamine 48 hours after transfection. There was a significant increase in BDNF release in cystamine-treated cells compared with control cells (post-hoc Fisher’s test, P = 0.0005). **P < 0.01, ^#P < 0.001.