Browsing by Author "Durrenberger, Pascal F."

Objectives. The role of neuroinflammation in schizophrenia has been an issue for long time. There are reports supporting the hypothesis of ongoing inflammation and others denying it. This may be partly ascribed to the origin of the materials (CSF, blood, brain tissue) or to the genes selected for the respective studies. Moreover, in some locations, inflammatory genes may be up-regulated, others may be down-regulated. Methods. Genome-wide microarrays have been used for expression profiling in post-mortem brains of schizophrenia patients. Array data have been analyzed by gene set enrichment analysis (GSEA) and further confirmed with selected genes by real-time PCR. Results. In Brodman Area 22 of left superior temporal cortex, at least 70 genes (19%) out of 369 down-regulated genes (P < 0.05) belonged to the immune system. 23 from those 70 genes were randomly selected for real-time PCR. Six reached significance level at P < 0.05. Conclusions. The present data support a brain-specific view of the role immune-modulatory genes may play in the left superior temporal cortex in schizophrenia, because immune functions in the patients are not disturbed. In keeping with comparable, previous studies supporting the notion that schizophrenia is a disease of the synapse, we hypothesize that dysregulation of immune-related genes modifies synaptic functions and stability in this region.

Inaccurate wiring and synaptic pathology appear to be major hallmarks of schizophrenia. A variety of gene products involved in synaptic neurotransmission and receptor signaling are differentially expressed in brains of schizophrenia patients. However, synaptic pathology may also develop by improper expression of intra- and extra-cellular structural elements weakening synaptic stability. Therefore, we have investigated transcription of these elements in the left superior temporal gyrus of 10 schizophrenia patients and 10 healthy controls by genome-wide microarrays (Illumina). Fourteen up-regulated and 22 downregulated genes encoding structural elements were chosen from the lists of differentially regulated genes for further qRT-PCR analysis. Almost all genes confirmed by this method were downregulated. Their gene products belonged to vesicle-associated proteins, that is, synaptotagmin 6 and syntaxin 12, to cytoskeletal proteins, like myosin 6, pleckstrin, or to proteins of the extracellular matrix, such as collagens, or laminin C3. Our results underline the pivotal roles of structural genes that control formation and stabilization of pre- and post-synaptic elements or influence axon guidance in schizophrenia. The glial origin of collagen or laminin highlights the close interrelationship between neurons and glial cells in establishment and maintenance of synaptic strength and plasticity. It is hypothesized that abnormal expression of these and related genes has a major impact on the pathophysiology of schizophrenia.