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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/11240

Title: Upregulation of CaMKIIβ and Nogo-C mRNA in Schizophrenia and the Prevalence of CAA Insert in the 3’UTR of the Nogo Gene
Authors: Novak, Gabriela
Advisor: Seeman, Philip
Department: Pharmacology
Keywords: CaMKII
schizophrenia
Nogo
RTN4
human
frontal cortex
gene variant
gene expression
Issue Date: 1-Aug-2008
Abstract: Schizophrenia may result from altered gene expression leading to abnormal neurodevelopment. In a search for genes with altered expression in schizophrenia, cDNA library subtractive hybridization experiments using post-mortem human frontal cerebral cortices from schizophrenia individuals and neurological controls were performed. I found the mRNA of two neurodevelopmentally important genes, Nogo (RTN4) and calcium/calmodulin-dependent protein kinase II beta (CaMKIIβ), to be overexpressed in post-mortem frontal cortex tissues from patients who suffered with schizophrenia. I used the quantitative real-time polymerase chain reaction method to determined the mRNA levels of these genes in tissues from age- and sex-matched individuals. Nogo is a myelin-associated protein which inhibits the outgrowth of neurites and nerve terminals. The gene produces three splice variants, Nogo-A, B and C. I found Nogo-C mRNA to be overexpressed by 26% in schizophrenia. I also found a 17% reduction of Nogo-B mRNA in samples from individuals who had been diagnosed with severe depression. Furthermore, I showed that there is a direct correlation between the expression of both Nogo-A and -C and the presence of a CAA insert in the 3’UTR of the Nogo gene. CaMKII is a kinase localized at the postsynaptic density. The holoenzyme is primarily composed of the subunits α and β, encoded by two separate genes. It influences the expression of many neuroreceptors, in particular receptors of the glutamatergic pathway. CaMKII also mediates neural maturation during puberty, a time of onset of schizophrenia. The expression of CaMKIIα was elevated 29% in frontal cortex tissues of patients who suffered from depression. The expression of CaMKIIβ was elevated 27% in tissues of schizophrenia patients and 36% in tissues of patients diagnosed with depression. Upregulation of CaMKIIβ was associated with the presence of the CAA insert in at least one copy of the Nogo gene in a group containing both healthy subjects and patients with mental illness, possibly linking the CaMKII and Nogo pathways. The values for the expression of Nogo, CaMKIIα and CaMKIIβ were normalized to β-glucuronidase expression to minimize the effects of mRNA degradation. These results confirm that upregulation of Nogo-C and CaMKIIβ is likely associated with schizophrenia.
URI: http://hdl.handle.net/1807/11240
Appears in Collections:Doctoral
Department of Pharmacology and Toxicology - Doctoral theses

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novak_gabriela_200801_PhD_thesis.pdfPh.D. Thesis2.28 MBAdobe PDF
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novak_gabriela_200801_PhD_appendix1.pdfAppendix 192.26 kBAdobe PDF
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novak_gabriela_200801_PhD_appendix2Appendix 2214.92 kBAdobe PDF
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novak_gabriela_200801_PhD_appendix3Appendix 3336.4 kBAdobe PDF
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novak_gabriela_200801_PhD_appendix4.pdfAppendix 4231.97 kBAdobe PDF
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