| 6181. |
- Larsson, Max, et al.
(författare)
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The sodium-dependent inorganic phosphate transporter SLC34A1 (NaPi-IIa) is not localized in the mouse brain : a case of tissue-specific antigenic cross-reactivity.
- 2011
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Ingår i: Journal of Histochemistry and Cytochemistry. - : Sage Publications. - 0022-1554 .- 1551-5044. ; 59:9, s. 807-812
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Tidskriftsartikel (refereegranskat)abstract
- The sodium-dependent inorganic phosphate transporter NaPi-IIa is expressed in the kidney. Here, the authors used a polyclonal antiserum raised against NaPi-IIa- and NaPi-IIa-deficient mice to characterize its expression in nervous tissue. Western blots showed that a NaPi-IIa immunoreactive band (~90 kDa) was only present in wild-type kidney membranes and not in kidney knockout or wild-type brain membranes. In the water-soluble fraction of wild-type and knockout brains, another band (~50 kDa) was observed; this band was not detected in the kidney. Light and electron microscopic immunohistochemistry using the NaPi-IIa antibodies showed immunolabeling of kidney tubules in wild-type but not knockout mice. In the brain, labeling of presynaptic nerve terminals was present also in NaPi-IIa-deficient mice. This labeling pattern was also produced by the NaPi-IIa preimmune serum. The authors conclude that the polyclonal antiserum is specific toward NaPi-IIa in the kidney, but in the brain, immunolabeling is caused by a cross-reaction of the antiserum with an unknown cytosolic protein that is not present in the kidney. This tissue-specific cross-reactivity highlights a potential pitfall when validating antibody specificity using knockout mouse-derived tissue other than the specific tissue of interest and underlines the utility of specificity testing using preimmune sera.
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| 6182. |
- Larsson, Max, et al.
(författare)
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Translocation of GluR1-containing AMPA receptors to a spinal nociceptive synapse during acute noxious stimulation.
- 2008
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Ingår i: Journal of Neuroscience. - Washington, DC, United States : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 28:28, s. 7084-7090
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Tidskriftsartikel (refereegranskat)abstract
- Potentiation of spinal nociceptive transmission by synaptic delivery of AMPA receptors, via an NMDA receptor- and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)-dependent pathway, has been proposed to underlie certain forms of hyperalgesia, the enhanced pain sensitivity that may accompany inflammation or tissue injury. However, the specific synaptic populations that may be subject to such plasticity have not been identified. Using neuronal tracing and postembedding immunogold labeling, we show that a model of acute inflammatory hyperalgesia is associated with an elevated density of GluR1-containing AMPA receptors, as well as an increased synaptic ratio of GluR1 to GluR2/3 subunits, at synapses established by C-fibers that lack the neuropeptide substance P. A more subtle increase in GluR1 immunolabeling was noted at synapses formed by substance P-containing nociceptors. No changes in either GluR1 or GluR2/3 contents were observed at synapses formed by low-threshold mechanosensitive primary afferent fibers. These results contrast with our previous observations in the same pain model of increased and decreased levels of activated CaMKII at synapses formed by peptidergic and nonpeptidergic nociceptive fibers, respectively, suggesting that the observed redistribution of AMPA receptor subunits does not depend on postsynaptic CaMKII activity. The present ultrastructural evidence of topographically specific, activity-dependent insertion of GluR1-containing AMPA receptors at a central synapse suggests that potentiation of nonpeptidergic C-fiber synapses by this mechanism contributes to inflammatory pain.
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| 6183. |
- Larsson, S. C., et al.
(författare)
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Serum magnesium and calcium levels in relation to ischemic stroke: Mendelian randomization study
- 2019
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 92:9, s. e944-e950
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether serum magnesium and calcium concentrations are causally associated with ischemic stroke or any of its subtypes using the mendelian randomization approach. METHODS: Analyses were conducted using summary statistics data for 13 single-nucleotide polymorphisms robustly associated with serum magnesium (n = 6) or serum calcium (n = 7) concentrations. The corresponding data for ischemic stroke were obtained from the MEGASTROKE consortium (34,217 cases and 404,630 noncases). RESULTS: In standard mendelian randomization analysis, the odds ratios for each 0.1 mmol/L (about 1 SD) increase in genetically predicted serum magnesium concentrations were 0.78 (95% confidence interval [CI] 0.69-0.89; p = 1.3 × 10-4) for all ischemic stroke, 0.63 (95% CI 0.50-0.80; p = 1.6 × 10-4) for cardioembolic stroke, and 0.60 (95% CI 0.44-0.82; p = 0.001) for large artery stroke; there was no association with small vessel stroke (odds ratio 0.90, 95% CI 0.67-1.20; p = 0.46). Only the association with cardioembolic stroke was robust in sensitivity analyses. There was no association of genetically predicted serum calcium concentrations with all ischemic stroke (per 0.5 mg/dL [about 1 SD] increase in serum calcium: odds ratio 1.03, 95% CI 0.88-1.21) or with any subtype. CONCLUSIONS: This study found that genetically higher serum magnesium concentrations are associated with a reduced risk of cardioembolic stroke but found no significant association of genetically higher serum calcium concentrations with any ischemic stroke subtype. Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
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| 6184. |
- Larsson, Sara, et al.
(författare)
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Neuroprotective effects of vitamin D on high fat diet- and palmitic acid-induced enteric neuronal loss in mice
- 2018
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Ingår i: BMC Gastroenterology. - : Springer Science and Business Media LLC. - 1471-230X. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The role of vitamin D in obesity and diabetes is debated. Obese and/or diabetic patients have elevated levels of free fatty acids, increased susceptibility to gastrointestinal symptoms and are suggested to have altered vitamin D balance. The enteric nervous system is pivotal in regulating gastrointestinal activity and high fat diet (HFD) has been shown to cause loss of enteric neurons in ileum and colon. This study investigates the effect of vitamin D on HFD- and palmitic acid-induced enteric neuronal loss in vivo and in vitro. METHODS: Mice were fed either a normal diet (ND) or HFD supplemented with varying levels of vitamin D (from 0x to 20x normal vitamin D level) for 19 weeks. Ileum and colon were analyzed for neuronal numbers and remodeling. Primary cultures of myenteric neurons from mouse small intestine were treated with palmitic acid (4x10-4M) and/or 1α,25-hydroxy-vitamin D3 (VD, 10-11- 10-7M) with or without modulators of lipid metabolism and VD pathways. Cultures were analyzed by immunocyto- and histochemical methods. RESULTS: Vitamin D supplementation had no effect on enteric neuronal survival in the ND group. HFD caused substantial loss of myenteric neurons in ileum and colon. Vitamin D supplementation between 0-2x normal had no effect on HFD-induced neuronal loss. Supplementation with 20x normal, prevented the HFD-induced neuronal loss. In vitro supplementation of VD prevented the palmitic acid-induced neuronal loss. The VD receptor (VDR) was not identified in enteric neurons. Enteric glia expressed the alternative VD receptor, protein disulphide isomerase family A member 3 (PDIA3), but PDIA3 was not found to mediate the VD response in vitro. Inhibition of peroxisome proliferator-activated receptor gamma (PPARγ) and immune neutralization of isocitrate lyase prevented the VD mediated neuroprotection to palmitic acid exposure. CONCLUSIONS: Results show that VD protect enteric neurons against HFD and palmitic acid induced neuronal loss. The mechanism behind is suggested to be through activation of PPARγ leading to improved neuronal peroxisome function and metabolism of neuronal lipid intermediates.
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| 6185. |
- Larsson, Susanna, et al.
(författare)
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Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae
- 2022
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Ingår i: Brain Sciences. - : MDPI AG. - 2076-3425. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future.
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| 6186. |
- Larsson, Staffan, 1969, et al.
(författare)
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TTR at the SPA: Relating type-theoretical semantics to neural semantic pointers
- 2023
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Ingår i: Proceedings of the 4th Natural Logic Meets Machine Learning Workshop. - 9781959429951
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Konferensbidrag (refereegranskat)abstract
- This paper considers how the kind of formal semantic objects used in TTR (a theory of types with records, Cooper, 2023) might be related to the vector representations used in Eliasmith (2013). An advantage of doing this is that it would immediately give us a neural representation for TTR objects as Eliasmith relates vectors to neural activity in his semantic pointer architecture (SPA). This would be an alternative using convolution to the suggestions made by Cooper (2019a) based on the phasing of neural activity. The project seems potentially hopeful since all complex TTR objects are constructed from labelled sets (essentially sets of ordered pairs consisting of labels and values) which might be seen as corresponding to the representation of structured objects which Eliasmith achieves using superposition and circular convolution.
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| 6187. |
- Larsson, Åsa, et al.
(författare)
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Increased cell proliferation and neurogenesis in the hippocampal dentate gyrus of old GFAP(-/-)Vim(-/-) mice
- 2004
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Ingår i: Neurochem Res. - : Springer Science and Business Media LLC. - 0364-3190. ; 29:11, s. 2069-73
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Tidskriftsartikel (refereegranskat)abstract
- In response to central nervous system (CNS) injury, and more discretely so also during aging, astrocytes become reactive and increase their expression of the intermediate filament proteins glial fibrillary acidic protein (GFAP) and vimentin. Studies of mice deficient in astrocytic intermediate filaments have provided insights into the function of reactive gliosis. Recently we demonstrated robust integration of retinal transplants (1) and increased posttraumatic synaptic regeneration (2) in GFAP(-/-)Vim(-/-) mice, suggesting that modulation of astrocyte activity affects the permissiveness of the CNS environment for regeneration. Neurogenesis in the adult mammalian CNS is restricted to essentially two regions, the hippocampus and the subventricular zone. Here, we assessed neurogenesis in the hippocampus of 18-month-old GFAP(-/-)Vim(-/-) mice. In the granular layer of the dentate gyrus, cell proliferation/survival was 34% higher and neurogenesis 36% higher in GFAP(-/-)Vim(-/-) mice than in wildtype controls. These findings suggest that the adult hippocampal neurogenesis in healthy old mice can be increased by modulating astrocyte reactivity.
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| 6188. |
- Lasič, Eva, et al.
(författare)
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Nestin affects fusion pore dynamics in mouse astrocytes.
- 2020
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Ingår i: Acta physiologica. - : Wiley. - 1748-1716 .- 1748-1708. ; 228:3
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Tidskriftsartikel (refereegranskat)abstract
- Astrocytes play a homeostatic role in the central nervous system and influence numerous aspects of neurophysiology via intracellular trafficking of vesicles. Intermediate filaments (IFs), also known as nanofilaments, regulate a number of cellular processes including organelle trafficking and adult hippocampal neurogenesis. We have recently demonstrated that the IF protein nestin, a marker of neural stem cells and immature and reactive astrocytes, is also expressed in some astrocytes in the unchallenged hippocampus and regulates neurogenesis through Notch signalling from astrocytes to neural stem cells, possibly via altered trafficking of vesicles containing the Notch ligand Jagged-1.We thus investigated whether nestin affects vesicle dynamics in astrocytes by examining single vesicle interactions with the plasmalemma and vesicle trafficking with high-resolution cell-attached membrane capacitance measurements and confocal microscopy. We used cell cultures of astrocytes from nestin-deficient (Nes-/- ) and wild-type (wt) mice, and fluorescent dextran and Fluo-2 to examine vesicle mobility and intracellular Ca2+ concentration respectively.Nes-/- astrocytes exhibited altered sizes of vesicles undergoing full fission and transient fusion, altered vesicle fusion pore geometry and kinetics, decreased spontaneous vesicle mobility and altered ATP-evoked mobility. Purinergic stimulation evoked Ca2+ signalling that was slightly attenuated in Nes-/- astrocytes, which exhibited more oscillatory Ca2+ responses than wt astrocytes.These results demonstrate at the single vesicle level that nestin regulates vesicle interactions with the plasmalemma and vesicle trafficking, indicating its potential role in astrocyte vesicle-based communication.
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| 6189. |
- Laska, Matthias
(författare)
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Olfactory Discrimination Learning in an Outbred and an Inbred Strain of Mice.
- 2015
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Ingår i: Chemical Senses. - : Oxford University Press. - 0379-864X .- 1464-3553. ; 40:7, s. 489-496
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Tidskriftsartikel (refereegranskat)abstract
- The present study compared olfactory discrimination learning in CD-1 mice, a widely used outbred strain of mice with that of C57BL/6J mice, one of the most widely used inbred mouse strains. Using an automated olfactometer and a standard operant conditioning procedure, I found that CD-1 mice needed 60 trials to reach learning criterion in an initial 2-odor discrimination task. They improved in learning speed in subsequent discrimination tasks in which either the rewarded or the unrewarded stimulus was replaced for a new stimulus. C57BL/6J mice, in contrast, needed 120 trials to reach learning criterion in an initial 2-odor discrimination task and also needed significantly more trials than the CD-1 mice in 3 of the 4 subsequent discrimination tasks. Further, the results showed that discrimination learning performance of both mouse strains was largely unaffected by the odor stimuli used. The results of the present study demonstrate differences between an outbred and an inbred strain of mice with regard to odor discrimination learning, a classical measure of cognitive performance in comparative psychology. Thus, they emphasize the need to be careful with generalizing statements as to cognitive or sensory abilities of Mus musculus when inbred strains of mice are used.
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| 6190. |
- Laskowski, Marta, 1991, et al.
(författare)
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Potassium-Channel-Independent Relaxing Influence of Adipose Tissue on Mouse Carotid Artery
- 2017
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Ingår i: Journal of Vascular Research. - : S. Karger AG. - 1018-1172 .- 1423-0135. ; 54:1, s. 51-57
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Tidskriftsartikel (refereegranskat)abstract
- Since the cardiovascular consequences of obesity reportedly vary in different types of obesity, we investigated the influence of adipose tissue from different locales on the phenylephrine- induced tone of the mouse carotid artery. Vessels were mounted in a Mulvany-Halpern-type wire myograph, and adipose tissue, from the back (brown) or mesenteric or inguinal subcutaneous (white), was placed around the artery. Contractile responses to phenylephrine were not affected by brown adipose tissue but were reduced (p < 0.001) by either type of white adipose tissue, with no difference between the 2 locales. The relaxing effect persisted in the presence of the Kv7 channel inhibitor XE991 (10,10-bis(4pyridinylmethyl)- 9(10H)-anthracenone), the K-ATP channel inhibitor glibenclamide (1 mu M), or the K-V channel inhibitor 4-amino pyridine (1 mM), as well as after elevation of the extracellular potassium concentration to 30 mM. Contractions of rat carotid artery were equally reduced by mouse and rat subcutaneous adipose tissue. Thus, white, but not brown, adipose tissue reduces the adrenergic contractions of the carotid artery with no differences between the locales of origin, and the effect appears largely independent of potassium channels.
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