| 1. |
- Davidsson, Pia, 1962, et al.
(författare)
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Clinical mass spectrometry in neuroscience. Proteomics and peptidomics.
- 2003
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Ingår i: Cellular and molecular biology (Noisy-le-Grand, France). - 0145-5680 .- 1165-158X. ; 49:5, s. 681-8
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Forskningsöversikt (refereegranskat)abstract
- In this review we discuss the merits and drawbacks with the use of proteomic and peptidomic strategies for identification of proteins and peptides in their multidimensional interactions in complex biological processes. The progress in proteomics and peptidomics during the last years offer us new challenges to study changes in the protein and peptide synthesis. These strategies also offer new tools to follow post-translational modifications and other disturbed chemical processes that may be indicative of pathophysiological alteration(s). Furthermore these techniques can contribute to improvements in the diagnosis and therapy of neurodegenerative diseases, such as Alzheimer's disease, and psychiatric diseases, as depression and post traumatic stress disorders. We also consider different practical aspects of the applications of mass spectrometry in clinical neuroscience, illustrated by example from our laboratories. The new proteomic and peptidomic strategies will further enable the progress for clinical neuroscience research.
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| 2. |
- Davidsson, Pia, 1962, et al.
(författare)
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Proteome analysis of cerebrospinal fluid proteins in Alzheimer patients.
- 2002
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Ingår i: Neuroreport. - : Ovid Technologies (Wolters Kluwer Health). - 0959-4965. ; 13:5, s. 611-5
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Tidskriftsartikel (refereegranskat)abstract
- By comparing the CSF proteome between Alzheimer disease (AD) patients and controls it may be possible to identify proteins that play a role in the disease process and thus to study the pathogenesis of AD. We used mini-gel technology in a two-dimensional electrophoresis procedure, sensitive SYPRO Ruby staining and mass spectrometry for clinical screening of disease-influenced CSF proteins in 15 AD patients and 12 controls. The levels of six proteins and their isoforms, including proapolipoprotein, apolipoprotein E, beta-2 microglobulin, retinol-binding protein, transthyretin, and ubiquitin, were significantly altered in CSF of AD patients. The most prominently altered proteins were the apolipoproteins, especially proapolipoprotein.
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| 3. |
- Davidsson, Pia, 1962, et al.
(författare)
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Proteome studies of human cerebrospinal fluid and brain tissue using a preparative two-dimensional electrophoresis approach prior to mass spectrometry.
- 2001
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Ingår i: Proteomics. - 1615-9853. ; 1:3, s. 444-52
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Tidskriftsartikel (refereegranskat)abstract
- A preparative proteomic approach, involving liquid phase isoelectric focusing (IEF) in combination with one-dimensional electrophoresis and electroelution followed by mass spectrometry and database searches, was found to be an important tool for identifying low-abundant proteins (microgram/L) in human cerebrospinal fluid (CSF) and membrane proteins in human frontal cortex. Several neuron-related proteins, such as amyloid precursor-like protein, chromogranins A and B, glial fibrillary acid protein, beta-trace, transthyretin, ubiquitin, and cystatin C, were identified in CSF. Several types of proteins were also characterized from a detergent-solubilized human frontal cortex homogenate including membrane proteins such as synaptophysin, syntaxin and Na+/K+ ATPase. One-third of the identified proteins have not previously been identified in human CSF or human frontal cortex using proteomic techniques. The absence of these proteins in two-dimensional electrophoresis maps might be due to insufficient amounts or low solubility. The advantages of using preparative liquid phase electrophoretic separations for identifying proteins from complex biological mixtures are speed of analysis, high loadability in the IEF separation, nondiscrimination of membrane proteins or low abundance proteins, yielding sufficient amounts for characterization by mass spectrometry. The use of this strategy in proteome studies of CSF/brain tissue is expected to offer new perspectives in studies of the pathology of neurodegenerative diseases, and reveal new potential markers for brain disorders.
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| 4. |
- 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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| 5. |
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| 6. |
- 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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| 7. |
- Paulson, Linda, 1971, et al.
(författare)
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Comparative genome- and proteome analysis of cerebral cortex from MK-801-treated rats.
- 2003
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012 .- 1097-4547. ; 71:4, s. 526-33
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Tidskriftsartikel (refereegranskat)abstract
- cDNA microarrays and two-dimensional gel-electrophoresis in combination with mass spectrometry, were used to screen alterations in mRNA and protein levels, respectively, in cerebral cortex of MK-801-treated rats. The rats were divided in two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, four genes were up-regulated and five down-regulated. In group 2, seven genes were up-regulated and six down-regulated. In group 1, the levels of one protein was increased and eight proteins reduced. In group 2, the levels of two proteins were increased and four proteins reduced. Several of the altered genes (casein kinase 2, glutamic acid decarboxylase, synaptotagmin, gamma aminobutyric acid [GABA] transporter, creatine kinase, and cytochrome c oxidase) and proteins (superoxide dismutase, hsp 60, hsp 72 and gamma-enolase) have previously been connected to schizophrenia. Alterations of the genes (microglobulin, c-jun proto-oncogene, 40S ribosomal protein S19, adenosine diphosphate (ADP)-ribosylation factors, platelet-derived growth factor, fructose-bisphophate aldolase A, and myelin proteolipid) and the proteins (stathmin, H+-transp. Adenosine triphosphate (ATP) synthase, pyruvate dehydrogenase, beta-actin and alpha-enolase), have not, to our knowledge, earlier been implicated in schizophrenia pathology. Overall, these results with a combined approach of genomics and proteomics add to the validity of subchronic N-methyl-D-aspartate (NMDA)-receptor antagonist treatment as an animal model of schizophrenia.
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| 8. |
- Paulson, Linda, 1971, et al.
(författare)
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Comparative proteome analysis of thalamus in MK-801-treated rats.
- 2004
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 4:3, s. 819-25
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Tidskriftsartikel (refereegranskat)abstract
- Two-dimensional gel-electrophoresis in combination with mass spectrometry is a powerful approach to compare protein expression in brain tissues. Using this proteomic approach, and based on the hypothesis that schizophrenia involves hypoglutamergic brain function, alterations in protein levels in the thalamus of rats treated with the N-methyl-D-aspartate (NMDA) receptor antagonist [+]-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]-cycloheptene-5,10-iminehydrogenmaleate (MK-801), as compared to saline-treated animals, were assessed in an unbiased fashion. The rats were divided into two groups; group 1 (short-term treated) and group 2 (long-term treated). In group 1, the levels of seven proteins were increased and four proteins reduced. In group 2, the levels of six proteins were reduced. Several of the altered proteins (heat shock proteins 60 and 72, albumin, dihydropyrimidinase related protein-2, aldolase c, and malate dehydrogenase) have previously been connected to schizophrenia. Alterations of other proteins (dihydrolipoamide acetyltransferase component of pyruvate dehydrogenase complex E2, guanine deaminase, alpha-enolase, aconitase, ATP-synthase and alpha-internexin), have not, to the best of our knowledge, earlier been implicated in schizophrenia pathology. Our results show the high potential of using proteomic methods for the validation of animal models of schizophrenia and to identify new proteins involved in the pathophysiological mechanisms of schizophrenia.
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| 9. |
- Paulson, Linda, 1971, et al.
(författare)
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Defining primary and secondary progenitor disorders in the brain: proteomic approaches for analysis of neural progenitor cells.
- 2007
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Ingår i: Current pharmaceutical biotechnology. - 1873-4316. ; 8:3, s. 117-25
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Forskningsöversikt (refereegranskat)abstract
- Since the discovery of endogenous progenitor cells in two brain regions in the adult, the notion that progenitor cells might be useful for repairing damaged neurons or replacing dead neurons has gone from fiction to a reality, at least in the laboratory setting. Progenitor cells have the unique ability to be able to produce new neurons in response to endogenous and exogenous cues from their microenvironment in the brain and from the environment of the organism. However, in models of several disorders and insults the regenerative potential of the central nervous system need external enhancing. In this review we begin by focussing on the developments in the field of neurobiology that have led to the specific study of neural progenitor cell biology. In particular we discuss the two germinal niches, the subventricular zone and the subgranular zone, as well as how various neurological diseases affect these niches. We furthermore try to define primary progenitor cell disorders and secondary progenitor cell responses. The second part of this review focuses on proteomic approaches for studying progenitor cells. These techniques allow the array of proteins that are expressed by progenitor cells to be determined and further more allow comparisons between diseased and normal cells or treated and untreated cell populations. If we can induce neural progenitor cells to generate functional neurons in the central nervous system (CNS) then the burden of neurological disorders may be eased in the future. The advances in proteomic technology have and will enable further understanding of the regulatory processes in these cells so that progenitor cell integration and differentiation can be enhanced. Hopefully an increase in knowledge of progenitor cell biology will have a major impact on clinical practice.
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| 10. |
- Paulson, Linda, 1971, et al.
(författare)
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Effect of levetiracetam on hippocampal protein expression and cell proliferation in rats.
- 2010
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Ingår i: Epilepsy research. - : Elsevier BV. - 1872-6844 .- 0920-1211. ; 90:1-2, s. 110-20
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Tidskriftsartikel (refereegranskat)abstract
- Levetiracetam (LEV) is a broad-spectrum antiepileptic drug (AED) with possibly also antiepileptogenic properties. LEV has a specific binding site in the central nervous system and reduces brain excitability; however, the precise mechanism of action (MOA) of LEV remains unclear. To further unravel the potential MOA pathways of LEV we investigated altered protein expression and cell proliferation in rat hippocampal tissue during LEV administration.
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