Journal
BRAIN BEHAVIOR AND IMMUNITY
Volume 23, Issue 5, Pages 573-579Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbi.2009.02.015
Keywords
Cytokines; Neuroinflammation; Neurodegeneration; Brain development; Learning
Categories
Funding
- Karolinska Institutet research funds
- Dementia Foundation
- Knut and Alice Wallenberg Foundation
- Gun and Bertil Stohne Foundation
- Swedish Brain Power programme
- Swedish Research Council [12194]
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The interleukin-1 (IL-1) family is unique in its including an endogenous antagonist of the IL-1 receptor (IL-1ra). IL-1ra has been shown to antagonise IL-1 signalling so effectively, that it came into clinical use within a few years from its discovery. Although barely detectable in the normal brain, IL-1 is dramatically upregulated during neuroinflammation, and also displays peaks of expression in the brain during development, as well as following the induction of long-term potentiation. IL-1 has been ascribed a central role in neuroinflammation accompanying ageing and age-related neurodegenerative conditions. Several experimental models based on genetically modified mice have been used in order to address the role of IL-1 in neurodegeneration and neuroprotection. Most of the findings here are based on the experiments involving a transgenic mouse strain with brain-directed overexpression of human IL-1ra, in which the balance between IL-1 and IL-1ra is permanently tipped towards inhibiting IL-1 signalling. The developmental effects of IL-1 are evident in the altered brain morphology in adult transgenic mice. In addition, IL-1 appears to be central in regulating the elasticity of the brain response to injury. Thus, a number of lines of evidence support the essential role played by IL-1 in development, plasticity, and physiological brain function. (C) 2009 Elsevier Inc. All rights reserved.
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