BRAIN TOLLS · Innate signals for brain homeostasis
6РП — Действия „Мария Кюри“
- Период
- 2006-01-01 → 2007-12-31
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- IRG
Линиите свързват координатора с партньорите. За проекти отпреди 2014 г. CORDIS не винаги дава точни координати. Тези точки са на ниво град или държава.
Накратко на български
Микроглиите в мозъка реагират на сигнали от увредени неврони, като например чрез специфични рецептори разпознават протеини, стимулирани от аденозин. Разбирането на тези процеси помага да се разбере как мозъкът сигнализира за възпаление и се стреми към възстановяване.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - BRAIN TOLLS (Innate signals for brain homeostasis)
The proposed research aimed to identify novel ligands that trigger microglial responses to brain injury. Microglia are cells that become activated in the injured or inflamed brain. A class of cell-signalling receptors called Toll-like receptors (TLRs) are suggested to recognise molecular entities generated in response to neuronal injury and to signal microglial response. This project examined expression of TLRs by microglia and identified molecules, released by neurons that triggered microglia via TLRs. In vivo data had shown selective and specific upregulation of TLR's by microglia in response to synaptic degeneration. Tissue culture systems were established to allow analysis of microglial responses to defined stimuli. Molecular affinity, antibody, and synthetic and pharmacologic agents were used in conjunction with genetically-modified microglia to define involvement of TLRs and to characterise potential agonist ligands. Results show that treatment of neurons with adenosine, a neuromodulator associated with injury responses, induced production of a novel lipoprotein moiety that acted through a TLR on microglia to signal for production of a cytokine (tumour necrosis factor-alpha) response.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Interaction between the immune and nervous systems is critical for repair, tumour surveillance and protection from infection. Toll-like receptors are evolutionarily ancient pattern-recognition receptors that are implicated in innate responses to infection. In work done in Canada we have shown that signals delivered through the Toll-like receptor-2 (TLR2) are critical for early microglial response to experimental brain injury. Microglia are macrophage-like cells in the brain and spinal cord that act as rapid sensors of loss of homeostasis of any kind. Activated microglia can recruit T cells and macrophages to the central nervous system via production of chemokines and cytokines.Our findings suggest that endogenous ligands for TLR2 are produced within the brain independent of infection and these ligands direct microglial response. This represents a novel role for TLR's in brain function. In Denmark, we propose to identify TLR2 ligands that are produced in response to injury in the mouse brain. Localized axona l degenerative injury will be used to induce TLR2 ligands. These will be assayed for their ability to induce intercellular signals, and mRNA and protein for specific cytokines and chemokines in microglial cultures.Criteria for functional TLR2 ligands will include purification with TLR2-Fc but not TLR4-Fc fusion proteins, and induction of responses in wild-type but not TLR2- or signalling-deficient microglia, that are blocked with TLR2- specific reagents. Ligands that meet these criteria will be characterized by proteomic analysis including 1- and 2-D gel electrophoresis, immunoblotting and mass spectrometry. Ligands are expected to be lipoproteins or peptidoglycans - our assays will detect both. Ligand-specific monoclonal antibodies will be generated and used to probe location and function. Long-term goals include gene manipulation in animal models.
Оригинален текст от CORDIS (на английски).
Участници
- UNIVERSITY OF SOUTHERN DENMARK (SYDDANSK UNIVERSITET) · ODENSE MКоординаторНиво градДания
Връзки
Данни: CORDIS, © Европейски съюз