| 1 | J. Neurosci. Res. 2009 Jan 87: 278-88 |
|---|---|
| PMID | 18683247 |
| Title | Evidence for disruption of sphingolipid metabolism in schizophrenia. |
| Abstract | As the field of glycobiology grows, important roles for glycolipids and glycoproteins in neurological disorders are being increasingly appreciated. However, few studies have explored the involvement of these molecules in the pathology of psychiatric illnesses. We investigated molecular differences related to glycobiology in subjects withschizophreniaby analyzing gene expression profiles using a focused glycogene chip, a custom-designed oligonucleotide array containing genes encoding proteins related to glycobiology, including glycosyltransferases, carbohydrate-binding proteins, proteoglycans, and adhesion molecules. We measured expression profiles in prefrontal cortical (BA46) samples fromschizophrenicsubjects and matched controls. We find differential expression of genes particularly related to glycosphingolipid/sphingolipid metabolism and N- and O-linked glycan biosynthesis in subjects withschizophrenia. Expression decreases of seven genes associated with these pathways, UGT8,SGPP1, GALC, B4GALT6, SPTLC2, ASAH1, and GAL3ST1, were validated by quantitative PCR inschizophrenicsubjects with short-term illness. Only one of these genes, SPTLC2, showed differential expression in chronicschizophrenicsubjects, although an increase in expression was observed. Covariate analysis showed that the expression of five of these genes was significantly positively correlated with age inschizophrenic, but not control, subjects. These changing patterns of expression could represent an adaptive response to pathology with disease progression or a compensatory effect of antipsychotic medication, although no significant correlations between gene expression levels and drug doses were observed. Disruption of sphingolipid metabolism early in illness could result in widespread downstream effects encompassing diverse pathological deficits already described inschizophrenia, especially those involving myelination and oligodendrocyte function; hence, this system may represent an important link inschizophreniapathology. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | J. Neurosci. Res. 2009 Jan 87: 278-88 |
| PMID | 18683247 |
| Title | Evidence for disruption of sphingolipid metabolism in schizophrenia. |
| Abstract | As the field of glycobiology grows, important roles for glycolipids and glycoproteins in neurological disorders are being increasingly appreciated. However, few studies have explored the involvement of these molecules in the pathology of psychiatric illnesses. We investigated molecular differences related to glycobiology in subjects withschizophreniaby analyzing gene expression profiles using a focused glycogene chip, a custom-designed oligonucleotide array containing genes encoding proteins related to glycobiology, including glycosyltransferases, carbohydrate-binding proteins, proteoglycans, and adhesion molecules. We measured expression profiles in prefrontal cortical (BA46) samples fromschizophrenicsubjects and matched controls. We find differential expression of genes particularly related to glycosphingolipid/sphingolipid metabolism and N- and O-linked glycan biosynthesis in subjects withschizophrenia. Expression decreases of seven genes associated with these pathways, UGT8,SGPP1, GALC, B4GALT6, SPTLC2, ASAH1, and GAL3ST1, were validated by quantitative PCR inschizophrenicsubjects with short-term illness. Only one of these genes, SPTLC2, showed differential expression in chronicschizophrenicsubjects, although an increase in expression was observed. Covariate analysis showed that the expression of five of these genes was significantly positively correlated with age inschizophrenic, but not control, subjects. These changing patterns of expression could represent an adaptive response to pathology with disease progression or a compensatory effect of antipsychotic medication, although no significant correlations between gene expression levels and drug doses were observed. Disruption of sphingolipid metabolism early in illness could result in widespread downstream effects encompassing diverse pathological deficits already described inschizophrenia, especially those involving myelination and oligodendrocyte function; hence, this system may represent an important link inschizophreniapathology. |
| SCZ Keywords | schizophrenia, schizophrenic |