Estradiol reverses excitatory synapse loss in a cellular model of neuropsychiatric disorders

摘要

Representative images of cortical neurons (DIV 26) transfected with GFP alone (control), GFP + HA-DISC1 or GFP + HA-DISC1ΔCT and treated with vehicle (Veh) or 17β-estradiol (E2) or not. Quantification of spine linear density. Treatment of control cells with 17β-estradiol resulted in an increase in spine number. Overexpression of HA-DISC1 or HA-DISC1ΔCT caused a significant reduction in spine linear density. Treatment with 17β-estradiol increased spine density in HA-DISC1 or HA-DISC1ΔCT expressing cells to a level not statistically different to vehicle control cells (dendritic spine linear density/10 µm): control, 5.8 ± 0.21; control + 17β-estradiol, 7.27 ± 0.44; HA-DISC1, 3.9 ± 0.2; HA-DISC1 + 17β-estradiol, 5.22 ± 0.34; HA-DISC1ΔCT, 3.4 ± 0.36; HA-DISC1ΔCT + 17β-estradiol, 5.5 ± 0.37). Representative images of DIV 26 cortical neurons expressing either HA-DISC1 or HA-DISC1ΔCT were treated with vehicle or 17β-estradiol for 30 min. Pseudo-color scheme is used to highlight regions where DISC1 clustering is occurring. Green arrow heads indicate DISC1 clusters in each condition. Quantification of DISC1 clustering; both HA-DISC1 or HA-DISC1ΔCT formed large clusters along dendrites. Treatment with 17β-estradiol reduced DISC1 clustering in neurons expressing either HA-DISC1 or HA-DISC1ΔCT. Scale bar = 5 µm.