Fig. 4: Chronic repeated treatment with 17β-estradiol (E2) rescues DISC1-induced spine deficits and reduces DISC1 aggregation.

a Schematic of chronic repeated 17β-estradiol (E2) treatment of either control or HA-DISC1ΔCT expressing neurons. Cortical neurons were transfected with GFP alone (control) or GFP and HA-DISC1ΔCT at DIV 17. Cells were treated daily with vehicle or 10 nM 17β-estradiol on DIV17–20. Neurons were fixed on DIV21. b Representative confocal images of DIV25 cortical neurons treated as in a. c Quantification of dendritic spine linear density. Chronic repeated treatment with 17β-estradiol increased in spine density in control cells. Ectopic expression of HA-DISC1ΔCT caused a significant reduction in spine linear density. Chronic repeated treatment with 17β-estradiol increased spine density in HA-DISC1ΔCT expressing cells to a level not statistically different to vehicle control cells. d Representative images of DIV 25 cortical neurons expressing either GFP alone or HA-DISC1ΔCT were treated with vehicle or 17β-estradiol daily between DIV17 and 24. Pseudo-color scheme is used to highlight regions where DISC1ΔCT clustering is occurring. e Quantification of DISC1 clustering. Chronic repeated treatment with 17β-estradiol reduced HA-DISC1ΔCT clustering. Scale bar = 5 µm.