| 1. |
- Hanrieder, Jörg, 1980, et al.
(författare)
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Time-of-Flight Secondary Ion Mass Spectrometry Based Molecular Histology of Human Spinal Cord Tissue and Motor Neurons
- 2013
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Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 85:18, s. 8741-8748
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Tidskriftsartikel (refereegranskat)abstract
- Secondary ion mass spectrometry is a powerful method for imaging biological samples with high spatial resolution. Whole section time-of-flight-secondary ion mass spectrometry (TOF-SIMS) scans and multivariate data analysis have been performed on the human spinal cord in order to delineate anatomical regions of interest based on their chemical distribution pattern. TOF-SIMS analysis of thoracic spinal cord sections was performed at 5 μm resolution within 2 h. Multivariate image analysis by means of principal component analysis and maximum auto correlation factor analysis resulted in detection of more than 400 m/z peaks that were found to be significantly changed. Here, the results show characteristic biochemical distributions that are well in line with major histological regions, including gray and white matter. As an approach for iterative segmentation, we further evaluated previously outlined regions of interest as identified by multivariate image analysis. Here, further discrimination of the gray matter into ventral, lateral, and dorsal neuroanatomical regions was observed. TOF-SIMS imaging has been carried out at submicrometer resolution obtaining localization and characterization of spinal motor neurons based on their chemical fingerprint, including neurotransmitter precursors that serve as molecular indicators for motor neuron integrity. Thus, TOF-SIMS can be used as an approach for chemical histology and pathology. TOF-SIMS holds immense potential for investigating the subcellular mechanisms underlying spinal cord related diseases including chronic pain and amyotrophic lateral sclerosis.
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| 2. |
- Hellström, Nina, 1976, et al.
(författare)
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Unique gene expression patterns indicate microglial contribution to neural stem cell recovery following irradiation.
- 2011
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Ingår i: Molecular and cellular neurosciences. - : Elsevier BV. - 1095-9327 .- 1044-7431. ; 46:4, s. 710-9
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Tidskriftsartikel (refereegranskat)abstract
- Ionizing radiation results in damage to neural stem cells and reduced neurogenesis. The aim of the present study was to determine intrinsic and extrinsic factors that influence neural stem cell survival following irradiation, using qPCR. Gene expression of hippocampal and SVZ neurospheres were analyzed following irradiation, and results demonstrated that irradiated hippocampal and SVZ stem cells displayed similar gene expression profiles for intrinsic genes. Irradiated microglia (extrinsic factor) isolated from the SVZ exhibited increased gene expression of growth factors involved in stem cell maintenance, proliferation, and survival. However, microglial genes in the irradiated hippocampus responded less favorably with respect to stem cell recovery. This might explain the superior recovery of SVZ compared to hippocampal stem cells following in vivo irradiation. In addition, our results show that a combination of growth factors, which were upregulated in SVZ microglia, increased the proliferation and decreased cell death of irradiated neurospheres in vitro.
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| 3. |
- Lindberg, Olle R, et al.
(författare)
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Characterization of Epidermal Growth Factor-Induced Dysplasia in the Adult Rat Subventricular Zone.
- 2012
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Ingår i: Stem cells and development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 21:8, s. 1356-1366
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Tidskriftsartikel (refereegranskat)abstract
- Epidermal growth factor (EGF) is a mitogen widely used when culturing adult neural stem cells in vitro. Although proliferative effects can also be observed in vivo, intracerebroventricular infusion of EGF has been found to counteract neuronal determination and promote glial differentiation instead. However, EGF receptor activation has different effects on the subventricular zone (SVZ) in mice and rats, possibly because of species differences in SVZ cell composition. Specifically in the rat, EGF stimulation of the SVZ induces the formation of hyperplastic polyps. The present study aims at molecular and morphological characterization of these subventricular polyps. Using immunohistochemistry, electron microscopy, and gene expression analysis, we demonstrate in hyperplastic EGF-induced polyps an upregulation in protein expression of Sox2, Olig2, GFAP, nestin, and vimentin. We found polyp-specific dysplastic changes in the form of coexpression of Sox2 and Olig2. This highly proliferative, Sox2/Olig2 coexpressing dysplastic cell type is >10-fold enriched in the hyperplastic polyps compared with control SVZ and most likely causes the polyp formation. Unique ultrastructural features of the polyps include a lack of ependymal cell lining as well as a large number of cells with large, light, ovoid nuclei and a cytoplasm with abundant ribosomes, whereas other polyp cells contain invaginated nuclei but fewer ribosomes. EGF also induced changes in the expression of Id genes Id1, Id2, and Id4 in the SVZ. Taken together, we here demonstrate dysplastic, structural, and phenotypical changes in the rat SVZ following EGF stimulation, which are specific to hyperplastic polyps.
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| 4. |
- Lindberg, Olle R, et al.
(författare)
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Effects of current alcohol use on brain volume among older adults in the Gothenburg H70 Birth Cohort study 2014-16
- 2024
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Ingår i: European Archives of Psychiatry and Clinical Neuroscience. - 0940-1334. ; 274:2, s. 363-373
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Tidskriftsartikel (refereegranskat)abstract
- Brain gray- and white matter changes is well described in alcohol-dependent elderly subjects; however, the effect of lower levels of alcohol consumption on the brain is poorly understood. We investigated the impact of different amounts of weekly alcohol consumption on brain structure in a population-based sample of 70-year-olds living in Gothenburg, Sweden. Cross-sectional data from 676 participants from The Gothenburg H70 Birth Cohort Study 2014-16 were included. Current alcohol consumers were divided into seven groups based on self-reported weekly amounts of alcohol consumption in grams (g) (0-50 g/week, used as reference group, 51-100 g/week, 101-150 g/week, 151-200 g/week, 201-250 g/week, 251-300 g/week, and > 300 g/week). Subcortical volumes and cortical thickness were assessed on T1-weighted structural magnetic resonance images using FreeSurfer 5.3, and white matter integrity assessed on diffusion tensor images, using tract-based statistics in FSL. General linear models were carried out to estimate associations between alcohol consumption and gray- and white matter changes in the brain. Self-reported consumption above 250 g/week was associated with thinning in the bilateral superior frontal gyrus, the right precentral gyrus, and the right lateral occipital cortex, in addition to reduced fractional anisotropy (FA) and increased mean diffusivity (MD) diffusively spread in many tracts all over the brain. No changes were found in subcortical gray matter structures. These results suggest that there is a non-linear relationship between alcohol consumption and structural brain changes, in which loss of cortical thickness only occur in non-demented 70-year-olds who consume more than 250 g/week.
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| 5. |
- Lindberg, Olle R, et al.
(författare)
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EGF-Induced Expansion of Migratory Cells in the Rostral Migratory Stream
- 2012
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9
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Tidskriftsartikel (refereegranskat)abstract
- The presence of neural stem cells in the adult brain is currently widely accepted and efforts are made to harness the regenerative potential of these cells. The dentate gyrus of the hippocampal formation, and the subventricular zone (SVZ) of the anterior lateral ventricles, are considered the main loci of adult neurogenesis. The rostral migratory stream (RMS) is the structure funneling SVZ progenitor cells through the forebrain to their final destination in the olfactory bulb. Moreover, extensive proliferation occurs in the RMS. Some evidence suggest the presence of stem cells in the RMS, but these cells are few and possibly of limited differentiation potential. We have recently demonstrated the specific expression of the cytoskeleton linker protein radixin in neuroblasts in the RMS and in oligodendrocyte progenitors throughout the brain. These cell populations are greatly altered after intracerebroventricular infusion of epidermal growth factor (EGF). In the current study we investigate the effect of EGF infusion on the rat RMS. We describe a specific increase of radixin(+)/Olig2(+) cells in the RMS. Negative for NG2 and CNPase, these radixin+/Olig2(+) cells are distinct from typical oligodendrocyte progenitors. The expanded Olig2(+) population responds rapidly to EGF and proliferates after only 24 hours along the entire RMS, suggesting local activation by EGF throughout the RMS rather than migration from the SVZ. In addition, the radixin+/Olig2(+) progenitors assemble in chains in vivo and migrate in chains in explant cultures, suggesting that they possess migratory properties within the RMS. In summary, these results provide insight into the adaptive capacity of the RMS and point to an additional stem cell source for future brain repair strategies.
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| 6. |
- Lindberg, Olle R, et al.
(författare)
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Epidermal growth factor treatment of the adult brain subventricular zone leads to focal microglia/macrophage accumulation and angiogenesis.
- 2014
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Ingår i: Stem cell reports. - : Elsevier BV. - 2213-6711. ; 2:4, s. 440-8
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Tidskriftsartikel (refereegranskat)abstract
- One of the major components of the subventricular zone (SVZ) neurogenic niche is the specialized vasculature. The SVZ vasculature isthought to be important in regulating progenitor cell proliferation and migration. Epidermal growth factor (EGF) is a mitogen witha wide range of effects. When stem and progenitor cells in the rat SVZ are treated with EGF, using intracerebroventricular infusion,dysplastic polyps are formed. Upon extended infusion, blood vessels are recruited into the polyps. In the current study we demonstrate how polyps develop through distinct stages leading up to angiogenesis. As polyps progress, microglia/macrophages accumulate in the polyp core concurrent with increasing cell death. Both microglia/macrophage accumulation and cell death peak during angiogenesis and subsequently decline following polyp vascularization. This model of inducible angiogenesis in the SVZ neurogenic niche suggests involvement of microglia/macrophages in acquired angiogenesis and can be used in detail to study angiogenesis inthe adult brain.
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| 7. |
- Olivecrona, Gunilla, et al.
(författare)
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Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia
- 2010
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Ingår i: Journal of Lipid Research. - New York : Rockefeller U.P.. - 0022-2275 .- 1539-7262. ; 51:6, s. 1535-1545
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Tidskriftsartikel (refereegranskat)abstract
- We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. Lipoprotein lipase (LPL) activity and mass in pre- and post-heparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [35S]Methionine incorporation studies on adipose tissue showed that newly synthesized LPL was normal in size and normally glycosylated. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids being derived from de novo lipogenesis, rather than from the plasma lipoproteins. Given the delayed release of LPL into the plasma after heparin, we suspected that the chylomicronemia might be caused by mutations in GPIHBP1. Indeed, all three affected siblings were compound heterozygotes for missense mutations involving highly conserved cysteines in the Ly6 domain of GPIHBP1 (C65S and C68G). The mutant GPIHBP1 proteins reached the surface of transfected CHO cells but were defective in their ability to bind LPL (as judged by both cell-based and cell-free LPL binding assays). Thus, the conserved cysteines in the Ly6 domain are crucial for GPIHBP1 function.
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| 8. |
- Persson, Åsa, 1980, et al.
(författare)
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Radixin inhibition decreases adult neural progenitor cell migration and proliferation in vitro and in vivo
- 2013
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Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Neuronal progenitors capable of long distance migration are produced throughout life in the subventricular zone (SVZ). Migration from the SVZ is carried out along a well-defined pathway called the rostral migratory stream (RMS). Our recent finding of the specific expression of the cytoskeleton linker protein radixin in neuroblasts suggests a functional role for radixin in RMS migration. The ezrin-radixin-moesin (ERM) family of proteins is capable of regulating migration through interaction with the actin cytoskeleton and transmembrane proteins. The ERM proteins are differentially expressed in the RMS with radixin and moesin localized to neuroblasts, and ezrin expression confined to astrocytes of the glial tubes. Here, we inhibited radixin function using the quinocarmycin analog DX52-1 which resulted in reduced neuroblast migration in vitro, while glial migration remained unaltered. Furthermore, the morphology of neuroblasts was distorted resulting in a rounded shape with no or short polysialylated neural cell adhesion molecule positive processes. Intracerebroventricular infusion of the radixin inhibitor resulted in accumulation of neuroblasts in the anterior SVZ. Neuroblast chains were short and intermittently interrupted in the SVZ and considerably disorganized in the RMS. Moreover, we studied the proliferation activity in the RMS after radixin inhibition, since concentrated radixin expression has been demonstrated in the cleavage furrow of dividing cells, which indicates a role of radixin in cell division. Radixin inhibition decreased neuroblast proliferation, whereas the proliferation of other cells in the RMS was not affected. Our results demonstrate a significant role for radixin in neuroblast proliferation and migration.
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| 9. |
- Trollberg, Olle, 1984-, et al.
(författare)
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On optimization of paper machines using economic model predictive control
- 2018
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Ingår i: Paper Conference and Trade Show, PaperCon 2018. - : TAPPI Press. - 9781510871892 ; , s. 286-293
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Konferensbidrag (refereegranskat)abstract
- In this paper we consider applying economic model predictive control (EMPC) for economic optimization of a paper machine. EMPC is used to optimize overall process targets, e.g., the economy, directly in the control layer. The basic idea in EMPC is that by combining a dynamic process-model with an economic model, it is possible to predict and optimize the future economic outcome with respect to the manipulated process variables. Periodically solving such an optimization problem with updated information from measurements corresponds to a feedback controller. The results presented here are based on simulations, using a grey-box model with parameters estimated from real data, that reveal that EMPC may improve several aspects of the economic performance of a paper machine. First, EMPC may automatically prioritize among an excessive number of inputs to determine which combinations of inputs to use in order to counter disturbances in the most economically efficient manner. Also, since EMPC makes use of dynamic optimization, it may utilize control inputs with zero steady-state gain which are not used for traditional set-point tracking. Second, since EMPC is predictive in nature, it may plan ahead and prepare the process for known changes such as grade-changes, hence reducing the transition-time with a significant reduction in production loss, and thereby significant improvements in profitability, especially for machines where grade-changes are frequent. Finally, we note that EMPC typically operates the process with constraints active, as is typical for economic optimization problems in general. This may cause problems with robustness since even small exogenous disturbances or unmodelled dynamics may cause constraint violations. We therefore suggest using an adaptive approach where a constraint margin is introduced in the EMPC optimization problem to ensure that the operating point is backed off from the actual constraints relevant for production, thereby improving the robustness.
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