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Contribution of systemic inflammation to chronic neurodegeneration

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Abstract

Systemic infection or inflammation gives rise to signals that communicate with the brain and leads to changes in metabolism and behaviour collectively known as sickness behaviour. In healthy young individuals, these changes are normally transient with no long-term consequences. The microglia are involved in the immune to brain signalling pathways. In the aged or diseased brain, the microglia have a primed phenotype as a consequence of changes in their local microenvironment. Systemic inflammation impacts on these primed microglia and switches them from a relatively benign to an aggressive phenotype with the enhanced synthesis of pro-inflammatory mediators. Recent evidence suggests that systemic inflammation contributes to the exacerbation of acute symptoms of chronic neurodegenerative disease and may accelerate disease progression. The normal homeostatic role that microglia play in signalling about systemic infections and inflammation becomes maladaptive in the aged and diseased brain and this offers a route to therapeutic intervention. Prompt treatment of systemic inflammation or blockade of signalling pathways from the periphery to the brain may help to slow neurodegeneration and improve the quality of life for individuals suffering from chronic neurodegenerative disease.

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Acknowledgments

The work in the author’s laboratory is supported by the Wellcome Trust, Medical Research Council (UK), Alzheimer’s Disease Society.

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  1. School of Biological Sciences, University of Southampton, Southampton General Hospital, Mail Point 840, LD80B, South Lab and Path Block, Southampton, SO16 6YD, UK

    V. Hugh Perry

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Perry, V.H. Contribution of systemic inflammation to chronic neurodegeneration. Acta Neuropathol 120, 277–286 (2010). https://doi.org/10.1007/s00401-010-0722-x

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