| 1. |
- Järlestedt, Katarina, et al.
(författare)
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Attenuation of reactive gliosis does not affect infarct volume in neonatal hypoxic-ischemic brain injury in mice
- 2010
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Ingår i: PLoS One. - 1932-6203. ; 5:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Astroglial cells are activated following injury and up-regulate the expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Adult mice lacking the intermediate filament proteins GFAP and vimentin (GFAP(-/-)Vim(-/-)) show attenuated reactive gliosis, reduced glial scar formation and improved regeneration of neuronal synapses after neurotrauma. GFAP(-/-)Vim(-/-) mice exhibit larger brain infarcts after middle cerebral artery occlusion suggesting protective role of reactive gliosis after adult focal brain ischemia. However, the role of astrocyte activation and reactive gliosis in the injured developing brain is unknown. METHODOLOGY/PRINCIPAL FINDINGS: We subjected GFAP(-/-)Vim(-/-) and wild-type mice to unilateral hypoxia-ischemia (HI) at postnatal day 9 (P9). Bromodeoxyuridine (BrdU; 25 mg/kg) was injected intraperitoneally twice daily from P9 to P12. On P12 and P31, the animals were perfused intracardially. Immunohistochemistry with MAP-2, BrdU, NeuN, and S100 antibodies was performed on coronal sections. We found no difference in the hemisphere or infarct volume between GFAP(-/-)Vim(-/-) and wild-type mice at P12 and P31, i.e. 3 and 22 days after HI. At P31, the number of NeuN(+) neurons in the ischemic and contralateral hemisphere was comparable between GFAP(-/-)Vim(-/-) and wild-type mice. In wild-type mice, the number of S100(+) astrocytes was lower in the ipsilateral compared to contralateral hemisphere (65.0+/-50.1 vs. 85.6+/-34.0, p<0.05). In the GFAP(-/-)Vim(-/-) mice, the number of S100(+) astrocytes did not differ between the ischemic and contralateral hemisphere at P31. At P31, GFAP(-/-)Vim(-/-) mice showed an increase in NeuN(+)BrdU(+) (surviving newly born) neurons in the ischemic cortex compared to wild-type mice (6.7+/-7.7; n = 29 versus 2.9+/-3.6; n = 28, respectively, p<0.05), but a comparable number of S100(+)BrdU(+) (surviving newly born) astrocytes. CONCLUSIONS/SIGNIFICANCE: Our results suggest that attenuation of reactive gliosis in the developing brain does not affect the hemisphere or infarct volume after HI, but increases the number of surviving newborn neurons.
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| 2. |
- Pekny, Tulen, et al.
(författare)
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Synemin is expressed in reactive astrocytes and Rosenthal fibers in Alexander disease
- 2014
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica. - : Wiley. - 0903-4641 .- 1600-0463. ; 122:1, s. 76-80
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Tidskriftsartikel (refereegranskat)abstract
- Alexander disease (AxD) is a neurodegenerative disorder with prominent white matter degeneration and the presence of Rosenthal fibers containing aggregates of glial fibrillary acidic protein (GFAP), and small stress proteins HSP27 and αB-crystallin, and widespread reactive gliosis. AxD is caused by mutations in GFAP, the main astrocyte intermediate filament protein. We previously showed that intermediate filament protein synemin is upregulated in reactive astrocytes after neurotrauma. Here, we examined immunohistochemically the presence of synemin in reactive astrocytes and Rosenthal fibers in two patients with AxD. There was an abundance of GFAP-positive Rosenthal fibers and widespread reactive gliosis in the white matter and subpial regions. Many of the GFAP-positive reactive astrocytes were positive for synemin, and synemin was also present in Rosenthal fibers. We show that synemin is expressed in reactive astrocytes in AxD, and is also present in Rosenthal fibers. The potential role of synemin in AxD pathogenesis remains to be investigated. © 2013 APMIS Published by Blackwell Publishing Ltd.
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| 3. |
- Shah, Faiz Ullah, et al.
(författare)
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Influence of Ferrocene and Transition Metals on the Biological Activities of Schiff Bases
- 2016
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Ingår i: Journal of the Chemical Society of Pakistan. - 0253-5106. ; 38:6, s. 1112-1120
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Tidskriftsartikel (refereegranskat)abstract
- A series of organic and organometallic Schiff bases bearing phenylferrocene and their six transition metal complexes have been prepared and tested for their potential biological applications by using antifungal, antibacterial, antitumor activities, toxicity testing against the brine shrimp and DNA damage analysis. The copper and cobalt complexes of organic Schiff base showed significant antibacterial activity. The antifungal activities tested against six fungal strains revealed that N-(4-hydroxybenzylidene) aniline (A5) had the highest antifungal activity. Most of these compounds showed cytotoxic activity against the brine shrimp. The results of showed that these compounds had significant antitumor activity, up to 97% in the case of N-(4-chlorobenzylidene) aniline (A3). Only two compounds N-(2-hydroxy benzylidene) 4-ferrocenylaniline (F2) and Nickel (II) complex of organic Schiff base (CO2) had DNA damaging activity at 20mg/ml concentration.
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| 4. |
- Ståhlberg, Anders, 1975, et al.
(författare)
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Defining cell populations with single-cell gene expression profiling: correlations and identification of astrocyte subpopulations.
- 2011
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Ingår i: Nucleic acids research. - : Oxford University Press (OUP). - 1362-4962 .- 0305-1048. ; 39:4
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Tidskriftsartikel (refereegranskat)abstract
- Single-cell gene expression levels show substantial variations among cells in seemingly homogenous populations. Astrocytes perform many control and regulatory functions in the central nervous system. In contrast to neurons, we have limited knowledge about functional diversity of astrocytes and its molecular basis. To study astrocyte heterogeneity and stem/progenitor cell properties of astrocytes, we used single-cell gene expression profiling in primary mouse astrocytes and dissociated mouse neurosphere cells. The transcript number variability for astrocytes showed lognormal features and revealed that cells in primary cultures to a large extent co-express markers of astrocytes and neural stem/progenitor cells. We show how subpopulations of cells can be identified at single-cell level using unsupervised algorithms and that gene correlations can be used to identify differences in activity of important transcriptional pathways. We identified two subpopulations of astrocytes with distinct gene expression profiles. One had an expression profile very similar to that of neurosphere cells, whereas the other showed characteristics of activated astrocytes in vivo.
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| 5. |
- Vardjan, N., et al.
(författare)
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IFN-gamma-induced increase in the mobility of MHC class II compartments in astrocytes depends on intermediate filaments
- 2012
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 9:Article Number: 144
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Tidskriftsartikel (refereegranskat)abstract
- Background: In immune-mediated diseases of the central nervous system, astrocytes exposed to interferon-gamma (IFN-gamma) can express major histocompatibility complex (MHC) class II molecules and antigens on their surface. MHC class II molecules are thought to be delivered to the cell surface by membrane-bound vesicles. However, the characteristics and dynamics of this vesicular traffic are unclear, particularly in reactive astrocytes, which overexpress intermediate filament (IF) proteins that may affect trafficking. The aim of this study was to determine the mobility of MHC class II vesicles in wild-type (WT) astrocytes and in astrocytes devoid of IFs. Methods: The identity of MHC class II compartments in WT and IF-deficient astrocytes 48 h after IFN-gamma activation was determined immunocytochemically by using confocal microscopy. Time-lapse confocal imaging and Alexa Fluor(546)-dextran labeling of late endosomes/lysosomes in IFN-gamma treated cells was used to characterize the motion of MHC class II vesicles. The mobility of vesicles was analyzed using ParticleTR software. Results: Confocal imaging of primary cultures of WT and IF-deficient astrocytes revealed IFN-gamma induced MHC class II expression in late endosomes/lysosomes, which were specifically labeled with Alexa Fluor(546)-conjugated dextran. Live imaging revealed faster movement of dextran-positive vesicles in IFN-gamma-treated than in untreated astrocytes. Vesicle mobility was lower in IFN-gamma- treated IF-deficient astrocytes than in WT astrocytes. Thus, the IFN-gamma-induced increase in the mobility of MHC class II compartments is IF-dependent. Conclusions: Since reactivity of astrocytes is a hallmark of many CNS pathologies, it is likely that the up-regulation of IFs under such conditions allows a faster and therefore a more efficient delivery of MHC class II molecules to the cell surface. In vivo, such regulatory mechanisms may enable antigen-presenting reactive astrocytes to respond rapidly and in a controlled manner to CNS inflammation.
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| 6. |
- Wilhelmsson, Ulrika, 1970, et al.
(författare)
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Astrocytes negatively regulate neurogenesis through the Jagged1-mediated notch pathway.
- 2012
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Ingår i: Stem cells (Dayton, Ohio). - : Oxford University Press (OUP). - 1549-4918 .- 1066-5099. ; 30:10, s. 2320-9
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Tidskriftsartikel (refereegranskat)abstract
- Adult neurogenesis is regulated by a number of cellular players within the neurogenic niche. Astrocytes participate actively in brain development, regulation of the mature central nervous system (CNS), and brain plasticity. They are important regulators of the local environment in adult neurogenic niches through the secretion of diffusible morphogenic factors, such as Wnts. Astrocytes control the neurogenic niche also through membrane-associated factors, however, the identity of these factors and the mechanisms involved are largely unknown. In this study, we sought to determine the mechanisms underlying our earlier finding of increased neuronal differentiation of neural progenitor cells when cocultured with astrocytes lacking glial fibrillary acidic protein (GFAP) and vimentin (GFAP(-/-) Vim(-/-) ). We used primary astrocyte and neurosphere cocultures to demonstrate that astrocytes inhibit neuronal differentiation through a cell-cell contact. GFAP(-/-) Vim(-/-) astrocytes showed reduced endocytosis of Notch ligand Jagged1, reduced Notch signaling, and increased neuronal differentiation of neurosphere cultures. This effect of GFAP(-/-) Vim(-/-) astrocytes was abrogated in the presence of immobilized Jagged1 in a manner dependent on the activity of γ-secretase. Finally, we used GFAP(-/-) Vim(-/-) mice to show that in the absence of GFAP and vimentin, hippocampal neurogenesis under basal conditions as well as after injury is increased. We conclude that astrocytes negatively regulate neurogenesis through the Notch pathway, and endocytosis of Notch ligand Jagged1 in astrocytes and Notch signaling from astrocytes to neural stem/progenitor cells depends on the intermediate filament proteins GFAP and vimentin.
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