Publikasjoner
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Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas
[Vis alle 21 forfattere av denne artikkelen]
(2017).
Exercise induces cerebral VEGF and angiogenesis via the lactate receptor HCAR1.
Nature Communications.
ISSN 2041-1723.
8.
doi:
10.1038/ncomms15557.
Fulltekst i vitenarkiv
Vis sammendrag
Physical exercise can improve brain function and delay neurodegeneration; however, the initial signal from muscle to brain is unknown. Here we show that the lactate receptor
(HCAR1) is highly enriched in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in pericyte-like cells along intracerebral microvessels. Activation of HCAR1 enhances cerebral vascular endothelial growth factor A (VEGFA) and cerebral angiogenesis. High-intensity interval exercise (5 days weekly for 7 weeks), as well as L-lactate subcutaneous injection that leads to an increase in blood lactate levels similar to exercise,
increases brain VEGFA protein and capillary density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle shows no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. Thus, we demonstrate that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.
Editorial summary:
Physical exercise promotes brain angiogenesis through an unknown signalling cascade. Morland et al. identify the elusive muscle-brain communication and show that lactate produced by muscle activity binds to its receptor HCAR1 in brain vessel-surrounding cells, stimulating VEGF production and brain angiogenesis.
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Reiten, Ingrid; Schlegel, Ulrike; Blixhavn, Camilla Hagen; Andersson, Krister Andreas; Aasebø, Ida Elisabeth Jørgensen & Yates, Sharon Christine
[Vis alle 12 forfattere av denne artikkelen]
(2020).
Data sharing through the online EBRAINS platform: a new service for brain research.
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Enhancing the reproducibility and transparency of research is an emerging theme across scientific disciplines, driven by new technological advances, and captured by the Open Science concept. The heterogeneity of research data, which often hinders direct comparisons of findings, adds a layer of complexity to this effort. To address these challenges in neuroscience, the Human Brain Project has developed a new research infrastructure, EBRAINS, providing tools and services to the neuroscientific community. The EBRAINS data curation service offers comprehensive stewardship for sharing experimental and computational data. New workflows and standards for neuroscience data and metadata management have been developed to make the research results discoverable, comparable across modalities, and possible to reanalyse and reuse in new combinations. Here we present our workflows and curation services tailored for sharing heterogeneous neuroscience data. We demonstrate the integration of such data in the infrastructure, and highlight some practicalities for researchers who want to share their neuroscience data through EBRAINS.
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Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Zehl, Lyuba; Zarfarnia, Sara; Köhnen, Stefan & Hilverling, Anna
[Vis alle 19 forfattere av denne artikkelen]
(2019).
Resources for making neuroscience data FAIR. The Human Brain Project invites researchers to share, find, and use data via the new EBRAINS infrastructure.
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Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Kleven, Heidi; Zehl, Lyuba; Bjerke, Ingvild Elise & Schmid, Oliver
[Vis alle 17 forfattere av denne artikkelen]
(2019).
Neuroinformatics platform for making neuroscience data Findable, Accessible, Interoperable, and Reuseable.
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Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Kleven, Heidi; Schlegel, Ulrike; Oliver, Schmid & Puchades, Maja
[Vis alle 10 forfattere av denne artikkelen]
(2019).
EBRAINS fair data service: A novel infrastructure for making neuroscience data findable, accessible, interoperable, and reuseable.
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Blixhavn, Camilla Hagen; Andersson, Krister Andreas; Kleven, Heidi; Schlegel, Ulrike; Puchades, Maja & Bjaalie, Jan G.
[Vis alle 7 forfattere av denne artikkelen]
(2019).
Find and explore rodent brain data using 3D atlases in the new EBRAINS infrastructure.
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Blixhavn, Camilla Hagen; Andersson, Krister Andreas; Kleven, Heidi; Schlegel, Ulrike; Puchades, Maja & Bjaalie, Jan G.
[Vis alle 7 forfattere av denne artikkelen]
(2019).
Infrastructure and workflow for integrating and navigating multi-scale and multi-modal murine neuroscience data using 3D digital brain reference atlases.
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Schlegel, Ulrike; Blixhavn, Camilla Hagen; Andersson, Krister Andreas; Yates, Sharon Christine; Øvsthus, Martin & Bjerke, Ingvild Elise
[Vis alle 11 forfattere av denne artikkelen]
(2019).
Integrating and analysing heterogeneous rodent neuroscience data using three-dimensional brain reference atlases.
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Achieving advances in the field of neuroscience with its rapidly growing number of published data requires integration across many scales and levels of investigation. Such integration is challenging due to the heterogeneous nature of the data, and the difficulty of comparing data from different studies. Key aspects include lack of standards for presentation of data and experimental parameters (metadata), and variable practices for assigning and reporting anatomical location in the brain. The EU Human Brain Project (HBP) is addressing these challenges by establishing an infrastructure of neuroinformatic tools and data curation services through which disparate neuroscience data can be shared, used and analysed. Three-dimensional (3D) open access brain reference atlases provide anatomical context for all the shared data, easing comparison and interpretation of findings. We here present HBP workflows for assigning metadata describing anatomical locations to different types of neuroscience data, and workflows for extracting, quantifying and co-visualizing morphological features from multiple datasets in 3D anatomical brain atlas viewers. We highlight the added value of mapping data to a common atlas framework in example studies, and demonstrate new analytic opportunities enabled by combining image analysis tools with information from a 3D brain reference atlas. The HBP now invites the community to use the new research infrastructure established.
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Andersson, Krister Andreas; Blixhavn, Camilla Hagen; Zehl, Lyuba; Markovic, Milica; Kleven, Heidi & Zafarnia, Sara
[Vis alle 15 forfattere av denne artikkelen]
(2018).
HBP Curation service: Share your data via the Neuroinformatics platform.
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Zehl, Lyuba; Zafarnia, Sara; Köhnen, Stefan; Andersson, Krister Andreas; Markovic, Milica & Legouée, Elodie
[Vis alle 20 forfattere av denne artikkelen]
(2018).
Integrating neuroscientific data into a unified database: from individual experiments to a standardized metadata collection using the Human Brain Project Neuroinformatics Platform.
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Zehl, Lyuba; Zafarnia, Sara; Köhnen, Stefan; Andersson, Krister Andreas; Markovic, Milica & Legouée, Elodie
[Vis alle 20 forfattere av denne artikkelen]
(2018).
Integrating neuroscientific data into a unified database: from individual experiments to a standardized metadata collection using the Human Brain Project Neuroinformatics Platform.
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Lambertus, Marvin; Sørli, Malin; Haugen, Øyvind Pernell; Andersson, Krister Andreas & Morland, Cecilie
(2018).
The effects of HCAR1 activation on the release of growth factors from pia mater fibroblasts.
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Øverberg, Linda Thøring; Andersson, Krister Andreas; Lambertus, Marvin; Hadzic, Alena; Haugen, Øyvind Pernell & Storm-Mathisen, Jon
[Vis alle 8 forfattere av denne artikkelen]
(2018).
Adult neurogenesis:
A regulatory role of lactate through the lactate receptor HCAR1?
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Bjerke, Ingvild Elise; Øvsthus, Martin; Andersson, Krister Andreas; Bjaalie, Jan G. & Leergaard, Trygve B.
(2018).
Best practices for determining and documenting neuroanatomical locations in the rodent brain.
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Blixhavn, Camilla Hagen; Andersson, Krister; Øvsthus, Martin; Bjerke, Ingvild Elise; Kleven, Heidi & Puchades, Maja
[Vis alle 8 forfattere av denne artikkelen]
(2018).
Data integration through digital brain atlasing: Making diverse neuroscience data discoverable using Human Brain Project infrastructure.
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Andersson, Krister Andreas; Bell, Simon; Bjerke, Ingvild Elise; Øvsthus, Martin; Blixhavn, Camilla Hagen & Kleven, Heidi
[Vis alle 18 forfattere av denne artikkelen]
(2017).
Submitting data and metadata through the HBP Data Workbench: Concepts, data flows, policies, and best practices.
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Bjerke, Ingvild Elise; Andersson, Krister Andreas; Øvsthus, Martin; Puchades, Maja ; Bjaalie, Jan G. & Leergaard, Trygve B.
(2017).
Navigating the rodent brain: Best practice recommendations for determining and documenting spatial location for neuroscience data .
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Andersson, Krister; Morland, Cecilie; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas
[Vis alle 21 forfattere av denne artikkelen]
(2017).
Exercise benefits brain through the lactate receptor HCAR1, increasing VEGF and capillary density in hippocampus and cortex.
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While physical exercise is known to improve brain function and delay neurodegeneration, the signal from muscle to brain has not been identified. We show here that the lactate receptor, hydroxycarboxylic acid receptor 1 (HCAR1 also known as GPR81), mediates exercise induced increase in the content of vascular endothelial growth factor A (VEGFA) and in capillary density in the hippocampus and cerebral cortex. Mice were subjected to high intensity interval exercise 5 days per week for 7 weeks. Increases in VEGFA and capillary density were observed in wild-type (wt) mice, but not in knockout (ko) mice lacking HCAR1. Subcutaneous injections of L-lactate 5 days per week for 7 weeks, to achieve intermittently high blood lactate levels comparable to those after exercise, reproduced the findings in wt mice. No changes were observed in ko mice. The intermittent nature of the stimulation may be important since continuously high extracellular lactate has previously been observed to down-regulate HCAR1. To our knowledge, the present finding is the first demonstration that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor. No changes in VEGFA or capillary density were observed in the cerebellar cortex. HCAR1 was highly expressed in pial fibroblast-like cells that line the vessels supplying blood to the brain, and in fibroblast-/pericyte-like cells along intracerebral microvessels. These cells are strategically placed to monitor changes in blood-born lactate as well as in brain extracellular lactate (which equilibrate across the vascular endothelium via monocarboxylate transporter 1). Skeletal muscle showed no vascular HCAR1 expression and no HCAR1-dependent change in vascularization induced by exercise or lactate. As VEGFA governs neuronal functions such as LTP as well as vascular growth, the increases may have direct effects on neurons as well as indirect effects through enhancement of vascularization. Both disturbed vascularization and impaired synaptic function are components of the pathogenesis in neurodegenerative dementias such as Alzheimer’s disease. The lactate receptor HCAR1 may prove a useful nutraceutical target for intervention in persons at risk for dementia who are unable to exercise sufficiently to achieve optimal HCAR1 stimulation through rises in blood lactate.
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Andersson, Krister; Morland, Cecilie; Haugen, Øyvind Pernell; Bergersen, Linda Hildegard & Storm-Mathisen, Jon
(2017).
Physical exercise promotes brain angiogenesis through a lactate receptor.
Vis sammendrag
Physical exercise can improve brain function and delay neurodegeneration, but the initial signal from muscle to brain is unknown. Here we show that the lactate receptor (HCAR1) is highly enriched in fibroblast-like cells that line and surround the pial blood vessels supplying the brain, and that activation of HCAR1 stimulates vascular endothelial growth factor A (VEGFA) levels and angiogenesis in hippocampus. High intensity interval exercise (five days weekly for seven weeks), as well as L-lactate injected subcutaneously to similarly increase blood lactate levels, caused a substantial increase in brain VEGFA protein and microvessel density in wild-type mice, but not in knockout mice lacking HCAR1. In contrast, skeletal muscle showed no vascular HCAR1 expression and no HCAR1 dependent change in vascularization induced by exercise or lactate. To our knowledge, this is the first demonstration that a substance released by exercising skeletal muscle induces supportive effects in brain through an identified receptor.
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Andersson, Krister; Øvsthus, Martin; Bjerke, Ingvild Elise; Puchades, Maja ; Telefont, Martin & Jeff, Muller
[Vis alle 9 forfattere av denne artikkelen]
(2017).
Data integration through digital brain atlasing: Human Brain Project infrastructure.
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The Human Brain Project is building an ICT-based scientific research infrastructure that will permit researchers to advance our knowledge in the fields of neuroscience through data exploration, analytics and simulation at multiple levels of brain organization. Experimental neuroscience is connected to the infrastructure through systems for organizing and managing heterogeneous research data. These data systems are initially tested by data producing laboratories in the HBP, and will ultimately be opened for the community. HBP data curation services support users in elevating the level of data consistency and in the migration of data to the open domain. The starting point for research projects that will use HBP resources is the HBP Collaboratory, a rich collaborative workspace which is open to the community. The Collaboratory provides guidance and access to resources, including storage for data and a workbench for entering and organizing metadata. As a central element, the Collaboratory provides high-quality reference atlases of the rodent and human brain, together with appropriate tools and workflows that allow users to register data to the atlases for their study, and to perform initial analysis of data. It also links to important external data repositories and services. Here we present an overview of currently available reference atlases, tools and workflows. We exemplify the use of these resources in a range of neuroscience projects, ranging from brain-wide mapping of molecular level information to identification of precise location of electrophysiology recording sites. With coordinates corresponding to reference atlas space, harvested through the workflow, valuable metadata for future search and analysis of data are captured. Furthermore, with data aligned to reference atlases, analysis of the spatial distribution of events, labeled elements, and regions of interest in image material is strongly supported. Following registration to reference atlas, subsequent image processing and analysis steps delivers lists of extracted features corresponding to atlas structures, enabling quantitative regional analysis. We exemplify analytical workflows producing automated quantification and spatial analysis of labeling in series of histological section images from whole rodent brain. These and other atlas related workflows will be made available as HBP software services.
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Bjerke, Ingvild Elise; Andersson, Krister; Øvsthus, Martin; Puchades, Maja ; Bjaalie, Jan G. & Leergaard, Trygve Brauns
(2017).
Determining and documenting the anatomical location of experimental neuroscience data: Best practice recommendations.
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Anatomical location is a key parameter for interpretation and comparison of neuroscientific data. Location is typically determined by looking up diagrams in anatomical reference atlases, communicated using anatomical terms, and shown in representative images. But the documentation provided varies considerably among scientific publications. Essential information about nomenclature and reference atlases, or criteria used to define boundaries of structures is often missing. This lack of accuracy limits the opportunities for comparing and integrating data from different publications, and could lead to failure in replicating scientific experiments. To clarify and address this challenge, we have investigated current practice for assigning and documenting anatomical location for different categories of experimental neuroscience data reported in > 120 articles investigating the rodent brain. Our findings show that the specificity and accuracy of anatomical documentation in most cases can be considerably improved with relatively simple procedures. We here suggest some general and method-specific recommendations for such improvements, and discuss how these steps may contribute to increase the accuracy of anatomical descriptions and data interpretation. We demonstrate how new three-dimensional rodent brain reference atlases, and associated software tools for spatial registration of brain image data to a common anatomical space, offer new opportunities for efficient integration and comparison of neuroscience data.
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Puchades, Maja ; Csúcs, Gergely; Checinska, Martyna; Øvsthus, Martin; Bjerke, Ingvild Elise & Andersson, Krister
[Vis alle 8 forfattere av denne artikkelen]
(2017).
Neuroinformatics tool and workflow for anchoring of serial histological images in rodent brain 3D space.
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Reference atlases of the brain are important tools for assigning location to data captured in neuroscience experiments. Spatial alignment of sectional images to reference atlases is, however, challenging to perform for several reasons. Manual approaches applied to large series of sectional images are time consuming and, moreover, histological sections are often cut at angles deviating from the principal anatomical planes presented in conventional reference atlases. Novel 3D reference atlases and accompanying tools provide new opportunities for rapid and accurate spatial registration and integration of data in common atlas space. We here present QuickNII which is new tools for use with the Waxholm Space atlas for the rat brain and the Allen Mouse brain atlas for the mouse brain, and a workflow that allows users to 1) interactively generate customized atlas images (slices of the 3D reference atlas) corresponding to the plane of sectioning of any experimental image series, 2) superimpose atlas images onto experimental images using affine transformations to match key anatomical landmarks, 3) propagate the transformations across a series of images, 4) assign spatial reference atlas coordinates to the experimental images, and 5) allow viewing and analysis of the experimental data integrated in the reference atlas. We exemplify the workflow and use of our methods with a range of experimental data from neuroanatomical and neurophysiological investigations.
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Puchades, Maja ; Øvsthus, Martin; Bjerke, Ingvild Elise; Andersson, Krister; Csúcs, Gergely & Leergaard, Trygve Brauns
[Vis alle 7 forfattere av denne artikkelen]
(2017).
Data integration through digital brain atlasing: semiautomatic spatial registration of serial histological images to rodent brain 3D reference atlases.
Vis sammendrag
Reference atlases of the brain are important tools for assigning location to data captured in neuroscience experiments. Spatial alignment of sectional images to reference atlases is, however, challenging to perform for several reasons. Manual approaches applied to large series of sectional images are time consuming and, moreover, histological sections are often cut at angles deviating from the principal anatomical planes presented in conventional reference atlases. Novel 3D reference atlases and accompanying tools provide new opportunities for rapid and accurate spatial registration and integration of data in common atlas space. We here present new tools for use with the Waxholm Space atlas for the rat brain and the Allen Mouse brain atlas, and workflow that allows users to 1) interactively generate customized atlas images (slices of the 3D reference atlas) corresponding to the plane of sectioning of any experimental image series, 2) superimpose atlas images onto experimental images using affine transformations to match key anatomical landmarks, 3) propagate the transformations across a series of images, 4) assign spatial reference atlas coordinates to the experimental images, and 5) allow viewing and analysis of the experimental data integrated in the reference atlas. We exemplify the work flow and use of our methods with a range of experimental data from neuroanatomical and neurophysiological investigations.
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Puchades, Maja ; Bjerke, Ingvild Elise; Øvsthus, Martin; Andersson, Krister; Csúcs, Gergely & Leergaard, Trygve Brauns
[Vis alle 7 forfattere av denne artikkelen]
(2016).
Spatial registration of serial histological image data to reference brain atlases.
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Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas
[Vis alle 18 forfattere av denne artikkelen]
(2016).
A novel mechanism for cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
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Hadzic, Alena; Andersson, Krister; Haugen, Øyvind Pernell; Storm-Mathisen, Jon; Stølen, Tomas & Wisløff, Ulrik
[Vis alle 8 forfattere av denne artikkelen]
(2016).
Lactate receptor HCAR1 mediates synaptic plasticity.
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Morland, Cecilie; Andersson, Krister; Haugen, Øyvind Pernell; Hadzic, Alena; Kleppa, Liv & Gille, Andreas
[Vis alle 18 forfattere av denne artikkelen]
(2016).
Exercise induces cerebral angiogenesis via lactate receptor HCAR1 at pial vessels.
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Publisert
6. sep. 2013 10:56
- Sist endret
6. sep. 2013 10:56