Figure 1.

p35 and p25-regulated proteins are downregulated in schizophrenia post-mortem brain. Total lysates of post-mortem samples from the hippocampus (A and B) and the prefrontal cortex (C and D) were western blotted against p35/p25, Cdk5, homer, PSD95 and the p25-regulated proteins septin 7 and OPA1. Protein levels were normalized against β-actin. Hippocampal total lysate from a p25 transgenic mouse (P25) was loaded as a control for specificity of staining on the western blots against p35/p25. (C) p35 and homer were decreased in hippocampus. However, in this tissue OPA1, but not septin 7, was reduced. Cdk5 levels remained unchanged. (D) There was a significant downregulation of p35, homer and septin 7 in prefrontal cortex of patients with schizophrenia. No changes were detected for OPA1, PSD95 or Cdk5 levels. (E and F) The downregulation of p35 was confirmed by immunohistochemistry on the prefrontal cortex (layer 3). (E) In control subjects, p35 antibody revealed evenly distributed labelling of moderate intensity in the neuronal cytoplasm and cell processes (arrows) with no significant nuclear staining. (F) In patients with schizophrenia, weak or absent cytoplasmic and cell process labelling was noted with moderate nuclear labelling. (G–H) Quantification of immunostaining against p35+25. (G) Somatic p35+p25 was strongly reduced in all prefrontal cortical layers in patients with schizophrenia. (H) Dendritic p35+p25 was reduced in layers 3, 5 and 6 of prefrontal cortex from patients with schizophrenia. (A and B): n = 13–15 per group; (C and D): n = 8–9 per group; (G and H): n = 95–105 cells per group. *P < 0.05; **P < 0.01; ***P < 0.001; average ± SEM is shown; (E and F): scale bar = 50 micrometer; 25 µm (insets). A.U = arbitrary units.