| 1 | ISRN Psychiatry 2013 -1 2013: 620361 |
|---|---|
| PMID | 23738220 |
| Title | Chronic phencyclidine increases synapsin-1 and synaptic adaptation proteins in the medial prefrontal cortex. |
| Abstract | Phencyclidine (PCP) mimics many aspects ofschizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5?mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5?mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, andMAPK1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data fromschizophrenicpatients and this further validates the use of phencyclidine in preclinical translational research. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 2 | ISRN Psychiatry 2013 -1 2013: 620361 |
| PMID | 23738220 |
| Title | Chronic phencyclidine increases synapsin-1 and synaptic adaptation proteins in the medial prefrontal cortex. |
| Abstract | Phencyclidine (PCP) mimics many aspects ofschizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5?mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5?mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, andMAPK1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data fromschizophrenicpatients and this further validates the use of phencyclidine in preclinical translational research. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 3 | Dev. Neurosci. 2015 -1 37: 43-55 |
| PMID | 25592202 |
| Title | Maternal immune activation induces changes in myelin and metabolic proteins, some of which can be prevented with risperidone in adolescence. |
| Abstract | Maternal infection is a risk factor forschizophreniabut the molecular and cellular mechanisms are not fully known. Myelin abnormalities are amongst the most robust neuropathological changes observed inschizophrenia, and preliminary evidence suggests that prenatal inflammation may play a role. Label-free liquid chromatography-mass spectrometry was performed on the prefrontal cortex (PFC) of adult rat offspring born to dams that were exposed on gestational day 15 to the viral mimic polyinosinic:polycytidylic acid [poly(I:C), 4 mg/kg] or saline and treated with the atypical antipsychotic drug risperidone (0.045 mg/kg) or saline in adolescence. Western blotting was employed to validate protein changes. Over 1,000 proteins were quantified in the PFC with pathway analyses implicating changes in core metabolic pathways, following prenatal poly(I:C) exposure. Some of these protein changes were absent in the PFC of poly(I:C)-treated offspring that subsequently received risperidone treatment in adolescence. Particularly interesting reductions in the expression of the myelin-related proteins myelin basic protein isoform 3 (MBP1) and rhombex 29 were observed, which were reversed by risperidone treatment. Validation by Western blotting confirmed changes in MBP1 and mitogen-activated kinase 1 (MAPK1). Western blotting was extended to assess the MAPK signalling proteins due to their roles in inflammation, namely phosphorylatedMAPK1和磷酸化MAPK-activated蛋白激酶2. Both were upregulated by poly(I:C) treatment and reversed by risperidone treatment. Overall, our data suggest that maternal inflammation may contribute to an increased risk forschizophreniathrough mechanisms involving metabolic function and myelin formation and that risperidone in adolescence may prevent or reverse such changes. |
| SCZ Keywords | schizophrenia, schizophrenic |
| 4 | Transl Psychiatry 2016 -1 6: e724 |
| PMID | 26836412 |
| Title | Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia. |
| Abstract | Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis ofschizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2,MAPK1and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessingschizophreniarisk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these fourschizophreniarisk-associated genes in 221 Caucasian subjects (89schizophreniapatients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found thatschizophrenia主题homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC inschizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease. |
| SCZ Keywords | schizophrenia, schizophrenic |