Fig 1: Targeting PLD and phosphatidic acid allows control of and long-term recovery from major depression. A and B, stress-induced effects on behavior (A) and hippocampal neurogenesis (B) and are reversed by i.v. injection of PLD or phosphatidic acid (PA). Vice versa, inhibition of PLD upon i.v. injection of the PLD inhibitor FIPI into nonstressed mice is sufficient to induce behavioral changes of major depression in these mice. C and D, injection of anti-ceramide antibodies clone S58-9 (anti-Cer), ceramidase (CDase), or phosphatidic acid results in a long-term correction of major depression in stressed mice. Mice were stressed for a total of 14 days, treated at day 7 and 10, and behavior (C) as well as neurogenesis (D) were determined 4 days after the second treatment. Shown are the mean ± SD from each eight (A and B) and six (C and D) animals/group. ∗∗∗p < 0.001, ANOVA and post hoc Tukey test. PLD, phospholipase D.
Fig 2: Ceramide inhibits endothelial PLD and reduces phosphatidic acid in the hippocampus. A and B, wildtype mice were stressed for 6 days with either glucocorticosterone (GC) or chronic unpredictable environmental stress (CUS) or were left untreated. On day 5, anti-ceramide IgM antibodies clone S58-9 (anti-Cer), control immunoglobulin M (ctrl IgM), recombinant ceramidase (CDase), recombinant PLD, or phosphatidic acid (PA) were i.v. injected. The hippocampus was removed 24 h after treatments and PLD activity (A), and the concentration of phosphatidic acid (B) were measured in total lysates of the hippocampus. C, treatment of bEnd3 or human brain-derived microvascular cells with 0.5 μM or 1 μM C24 ceramide results in inhibition of PLD activity and reduces cellular phosphatidic acid concentrations. Shown are the mean ± SD from each eight animals/group (A and B) or eight independent experiments (C). ∗∗∗p < 0.001, ANOVA and post hoc Tukey test. PLD, phospholipase D.
Supplier Page from Abcam for Recombinant Human GPI-PLD protein (GST tag N-Terminus)