| 1. |
- Lindström, L, et al.
(författare)
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Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia.
- 2005
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Ingår i: Schizophrenia research. - : Elsevier BV. - 0920-9964 .- 1573-2509. ; 80:2-3, s. 315-22
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that endogenous brain levels of kynurenic acid (KYNA), a glutamate receptor antagonist, are elevated in patients with schizophrenia. Here we analyse KYNA in the cerebrospinal fluid (CSF) from a large cohort, including male healthy controls (n=49) and male patients with schizophrenia (n=90). We found that male patients with schizophrenia had significantly higher levels of CSF KYNA compared to healthy male controls (1.45 nM+/-0.10 vs. 1.06 nM+/-0.06 in the control group). Furthermore, when the patients with schizophrenia were divided into subgroups we found that CSF KYNA levels were significantly elevated in drug-naïve, first episode patients (1.53 nM+/-0.19, n=37) and in patients undergoing treatment with antipsychotic drugs (1.53 nM+/-0.17, n=34) compared to healthy male controls. No elevated CSF KYNA levels were detected in drug-free patients with schizophrenia, i.e. patients previously undergoing antipsychotic medications but drug-free at time of sampling (1.16 nM+/-0.10, n=19). Present results confirm that CSF KYNA concentration is elevated in patients with schizophrenia and are consistent with the hypothesis that KYNA contributes to the pathophysiology of the disease.
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| 2. |
- Paulson, Linda, 1971
(författare)
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Comparative genome and proteome analysis of brain tissue from MK-801-treated rats
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Symptoms of intoxication with non-competitive N-methyl-D-aspartate (NMDA)-receptor antagonists, closely mimic symptoms in patients with schizophrenia, and therefore [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10-iminehydrogen-maleate (MK-801, dizocilpine) treated rodents are often used as a model for schizophrenia. To investigate if administration of the NMDA receptor antagonist MK-801 to rats would induce messenger ribonucleic acid (mRNA) or protein disturbances mimicking those observed in schizophrenic patients, complementary deoxyribonucleic acid (cDNA) microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry were used, respectively. MK-801-induced changes in mRNA and protein levels were screened in the cortex, and protein levels in the thalamus, of MK-801-treated rats. Some of the altered proteins were unique for this model, and some previously found to be associated with schizophrenia were identified, displaying the utility of genomic and proteomic methods for biochemical studies on MK-801-treated rats as a model for schizophrenia. However, different proteins were altered at different treatment times of MK-801. For this reason, a study was designed to analyze how acute and subchronic MK-801-treatment to rats affected the protein profiles on rat thalamic proteome. Our results showed that the levels of many proteins were unaffected after one acute injection of MK-801 and that different treatment times of MK-801 to rats gave altered protein patterns. The effects of protein levels in thalamus of one typical (haloperidol) and one atypical (clozapine) antipsychotic on MK-801-treated rats were studied to investigate if these antipsychotic compounds would reverse the development of biochemical disturbances found in MK-801-treated rats. The protein changes induced by MK-801 treatment were reversed by clozapine and haloperidol in thalamus. In cortex, clozapine reversed all three protein changes induced by MK-801, and haloperidol reversed two out of three protein changes. In conclusion, proteomic and genomic studies on MK-801-treated rodents show a potential for further evaluating the MK-801 model of schizophrenia, by studying gene and protein alterations in the brain.
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| 3. |
- Paulson, Linda, 1971, et al.
(författare)
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Proteomics and peptidomics in neuroscience. Experience of capabilities and limitations in a neurochemical laboratory.
- 2005
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Ingår i: Journal of mass spectrometry : JMS. - : Wiley. - 1076-5174 .- 1096-9888. ; 40:2, s. 202-13
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Forskningsöversikt (refereegranskat)abstract
- The increasing use of proteomics has created a basis for new strategies to develop methodologies for rapid identification of protein patterns in living organisms. It has also become evident that proteomics has other potential applications than protein and peptide identification, e.g. protein characterization, with the aim of revealing their structure, function(s) and interactions of proteins. In comparative proteomics studies, the protein expression of a certain biological system is compared with another system or the same system under perturbed conditions. Global identification of proteins in neuroscience is extremely complex, owing to the limited availability of biological material and very low concentrations of the molecules. Moreover, in addition to proteins, there are number of peptides that must also be considered in global studies on the central nervous system. In this overview, we focus on and discuss problems related to the different sources of biological material and sample handling, which are part of all preparatory and analytical steps. Straightforward protocols are desirable to avoid excessive purification steps, since loss of material at each step is inevitable. We would like to merge the two worlds of proteomics/peptidomics and neuroscience, and finally we consider different practical and technical aspects, illustrated with examples from our laboratory.
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