Nogo A, B and C expression in schizophrenia, depression and bipolar frontal cortex, and correlation of Nogo...

Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, our previous work on human frontal cerebral cortex found the mRNA of Nogo, a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals, to be overexpressed in schizophrenia. Because those earlier results did not examine tissues for the separate Nogo A, B and C isoforms from age- and sex-matched individuals, we repeated the study for all three isoforms, using a new set of tissues from matched individuals, and using the more accurate method of quantitative real-time PCR (polymerase chain reaction). We found Nogo C to be overexpressed by 26% in the schizophrenia tissues, which is in accordance with our earlier results. The expression of Nogo B was statistically significantly reduced by 17% in the frontal cortices from individuals who had been diagnosed as having had severe depression. Furthermore, we show that there is a direct correlation between the expression of Nogo A and C and the presence of alleles with a CAA insert, irrespective of disease status. While upregulation of Nogo C expression may play a role in schizophrenia, altered Nogo B may contribute to the clinical condition of depression. Nogo A showed a statistically non-significant increase in expression in schizophrenia.