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The impact of systemic inflammation on the brain in health and disease| old_uid | 4547 |
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| title | The impact of systemic inflammation on the brain in health and disease |
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| start_date | 2008/04/07 |
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| schedule | 11h30 |
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| online | no |
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| details | Séminaire labelisé INB / Ecole doctorale / AXE Neuroinflammation |
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| summary | We have all at one time or another experienced the consequences of a systemic infection, we have felt ill – we have experienced sickness behaviour. A number of routes have been identified by which systemic inflammation communicates with the brain and this includes both neural and humoral routes. Within the brain the signals that convey information about systemic inflammation involve immune cells of the brain, the macrophages and microglia, and the communication between non-neuronal cells and neurons involves molecules that are themselves inflammatory mediators such as cytokines and prostaglandins. In the normal healthy brain the microglia are kept under tight regulation by the CNS microenvironment and are commonly thought of as having a downregulated phenotype. However, following chronic or acute neurodegeneration the microglia become activated or “primed”. We have been interested to learn how systemic inflammation may impact on the diseased brain to either exacerbate sickness behaviour or the chronic neurodegenerative disease.
Using murine prion disease as a model of chronic neurodegeneration we have shown that the activated microglia adopt a phenotype that is dominated by the presence of TGF-b1, COX-2 and MCP-1. This phenotype appears early in disease and is associated with the loss of synapses and the presence of misfolded PrPsc. We have no evidence that these cells significantly contribute to disease progression following intracerebral initiation of the disease. To mimic a systemic infection mice with prion disease were challenged systemically with LPS: the microglia rapidly switch their phenotype to an aggressive pro-inflammatory phenotype and synthesised pro-inflammatory cytokines. The onset of pro-inflammatory cytokine synthesis is associated with an exaggerated sickness behaviour response and increased neuronal degeneration. We have hypothesised that systemic infections in diseases such as Alzheimer’s disease will exacerbate acute symptoms of sickness behaviour and accelerate disease progression. Our recent clinical studies show that common systemic infections have a profound effect on patients with Alzheimer’s disease. |
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| responsibles | Deris |
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