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Recent mouse studies of the presymptomatic stage of Alzheimer's disease (AD) have suggested that proinflammatory changes, such as glial activation and cytokine induction, may occur already at this early stage through unknown mechanisms. Because TNFα contributes to increased Aβ production from the Aβ precursor protein (APP), we assessed a putative correlation between APP/Aβ and TNFα during the presymptomatic stage as well as early astrocyte activation in the hippocampus of 3-month-old APPswe/PS1dE9 mice. While Western blots revealed significant APP expression, Aβ was not detectable by Western blot or ELISA attesting that 3-month-old, APPswe/PS1dE9 mice are at a presymptomatic stage of AD-like pathology. Western blots were also used to show increased GFAP expression in transgenic mice that positively correlated with both TNFα and APP, which were also mutually correlated. Subregional immunohistochemical quantification of phenotypic (GFAP) and functional (TSPO) markers of astrocyte activation indicated a selective and significant increase in GFAP-immunoreactive (IR) cells in the dentate gyrus of APPswe/PS1dE9 mice. Our data suggest that subtle morphological and phenotypic alterations, compatible with the engagement of astrocyte along the activation pathway, occur in the hippocampus already at the presymptomatic stage of AD.
", "funding": [ { "award": { "acronym": "INMIND", "id": "00k4n6c32::278850", "identifiers": [ { "identifier": "https://cordis.europa.eu/projects/278850", "scheme": "url" } ], "number": "278850", "program": "FP7", "title": { "en": "Imaging of Neuroinflammation in Neurodegenerative Diseases" } }, "funder": { "id": "00k4n6c32", "name": "European Commission" } } ], "publication_date": "2016-09-08", "publisher": "Zenodo", "resource_type": { "id": "publication-article", "title": { "de": "Zeitschriftenartikel", "en": "Journal article" } }, "rights": [ { "description": { "en": "The Creative Commons Attribution license allows re-distribution and re-use of a licensed work on the condition that the creator is appropriately credited." }, "icon": "cc-by-icon", "id": "cc-by-4.0", "props": { "scheme": "spdx", "url": "https://creativecommons.org/licenses/by/4.0/legalcode" }, "title": { "en": "Creative Commons Attribution 4.0 International" } } ], "title": "Expression of Phenotypic Astrocyte Marker Is Increased in a Transgenic Mouse Model of Alzheimer's Disease versus Age-Matched Controls: A Presymptomatic Stage Study." }, "parent": { "access": { "owned_by": { "user": 1964 } }, "communities": { "default": "724cc757-0e37-4b01-a81f-b8aa5f1d7b44", "entries": [ { "access": { "member_policy": "open", "members_visibility": "public", "record_policy": "open", "review_policy": "open", "visibility": "public" }, "children": { "allow": false }, "created": "2014-01-06T13:42:25+00:00", "custom_fields": {}, "deletion_status": { "is_deleted": false, "status": "P" }, "id": "724cc757-0e37-4b01-a81f-b8aa5f1d7b44", "links": {}, "metadata": { "curation_policy": "all uploads acknowledging the INMiND project are accepted", "page": "The goal of the EC FP7 Collaborative Project INMiND (GA 278850) is to carry out collaborative research on molecular mechanisms that link neuroinflammation with neurodegeneration in order to identify novel biological targets for activated microglia, which may serve for both diagnostic and therapeutic purposes, and to translate this knowledge into clinical application and patient benefit.
\r\n\r\n\r\n\r\n
The general objectives of INMiND are:
\r\n\r\n(i) to identify novel mechanisms of regulation and function of microglia under various conditions (inflammatory stimuli; neurodegenerative and -regenerative model systems);
\r\n\r\n(ii) to identify and implement new targets for activated microglia, which may serve for diagnostic (imaging) and therapeutic purposes;
\r\n\r\n(iii) to design new molecular probes (tracers) for these novel targets and to implement and validate them in in vivo innovative model systems and in patients;
\r\n\r\n(iv) to image and quantify modulated microglia activity in patients undergoing immune therapy for cognitive impairment, and to relate the findings to clinical outcome.
\r\n\r\nThe INMiND projects brings together a group of excellent basic scientists and clinicians with a proven background in efficiently accomplishing common scientific goals (FP6 DiMI, www.dimi.eu), who belong to highly complementary fields of research (from genome-oriented to imaging scientists and clinicians), and who are dedicated to formulate novel image-guided therapeutic strategies for neuroinflammation-related neurodegenerative diseases.
\r\n\r\nThe strength of the project is that, across Europe, it coordinates research and training activities related to neuroinflammation, neurodegeneration, neuroregeneration, and imaging with special emphasis on translating basic mechanisms into clinical applications that shall provide health benefits for our aging population.
\r\n\r\nWith its intellectual excellence and its crucial mass the INMiND consortium is playing a major role in the European Research Area and will gain European leadership in the creation of new image-guided diagnosis and therapy paradigms in patients with neurodegenerative diseases.
", "title": "INMiND - Imaging of Neuroinflammation in Neurodegenerative Diseases" }, "revision_id": 0, "slug": "inmind", "updated": "2016-09-28T07:01:51.111318+00:00" }, { "access": { "member_policy": "open", "members_visibility": "restricted", "record_policy": "open", "review_policy": "closed", "visibility": "public" }, "children": { "allow": true }, "created": "2022-11-23T15:53:29.436323+00:00", "custom_fields": {}, "deletion_status": { "is_deleted": false, "status": "P" }, "id": "f0a8b890-f97a-4eb2-9eac-8b8a712d3a6c", "links": {}, "metadata": { "curation_policy": "The EU Open Research Repository serves as a repository for research outputs (data, software, posters, presentations, publications, etc) which have been funded under an EU research funding programme such as Horizon Europe, Euratom or earlier Framework Programmes.
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\nZenodo’s general policies and Terms of Use apply to all content.
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\nSubjects: Records SHOULD specify one or more fields of science from the European Science Vocabulary.
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", "description": "Open repository for EU-funded research outputs from Horizon Europe, Euratom and earlier Framework Programmes.", "organizations": [ { "id": "00k4n6c32" } ], "page": "The EU Open Research Repository is a Zenodo-community dedicated to fostering open science and enhancing the visibility and accessibility of research outputs funded by the European Union. The community is managed by CERN on behalf of the European Commission.
\nThe mission of the repository is to support the implementation of the EU's open science policy, providing a trusted and comprehensive space for researchers to share their research outputs such as data, software, reports, presentations, posters and more. The EU Open Research Repository simplifies the process of complying with open science requirements, ensuring that research outputs from Horizon Europe, Euratom, and earlier Framework Programmes are freely accessible, thereby accelerating scientific discovery and innovation.
\nThe EU Open Research Repository serves as a complementary platform to the Open Research Europe (ORE) publishing platform. Open Research Europe focuses on providing a publishing venue for peer-reviewed articles, ensuring that research meets rigorous academic standards. The EU Open Research Repository provides a space for all the other research outputs including data sets, software, posters, and presentations that are out of scope for ORE. This holistic approach enables researchers to not only publish their findings but also share the underlying data and materials that support their work, fostering transparency and reproducibility in the scientific process.
\nCurrently in its pilot phase and set to be fully operational during autumn 2024, the EU Open Research Repository is constantly evolving. Efforts are committed to integrating cutting-edge features, including automated curation checks and FAIR (Findable, Accessible, Interoperable, and Reusable) assistance, to further support the research community. The goal is to provide researchers with a simple goto solution for making their publicly funded research open and as FAIR as possible.
\nThe EU Open Research Repository is funded by the European Union under grant agreement no. 101122956(HORIZON-ZEN). For more information about the project see https://about.zenodo.org/projects/horizon-zen/.
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