Abnormal pathways in the genu of the corpus callosum in schizophrenia pathogenesis: a proteome study

Abnormalities within the corpus callosum (CC) have been identified in schizophrenia brains and are thought to affect inter-hemispheric communication, which in-turn is postulated to underlie some schizophrenia symptoms. Furthermore, hemisphere asymmetry of fractional anisotropy, detected by diffusion tensor imaging, left-higher-than-right- has been observed in normal individuals in the CC genu. This asymmetry is significantly reduced in the left CC genu of first-episode and chronic schizophrenia subjects. We examined the protein expression profile of the CC genu, including the profiles from the left and right hemisphere, in schizophrenia brains compared to controls using two-dimensional gel electrophoresis and mass spectrometry techniques. Proteins involved in cytoskeletal structure and function, neuroprotective function and energy metabolism were identified as differentially expressed, suggesting these proteins may underlie abnormal CC genu structure and function. Proteins in these functional categories also displayed different expression levels in the left CC genu compared to the right in both control and schizophrenia brains and therefore may be involved in normal CC asymmetry and reduced asymmetry in schizophrenia individuals. This initial pool of protein candidates and abnormal functional pathways opens up avenues for further investigation of molecular mechanisms involving the CC in schizophrenia pathogenesis and symptoms.