Blunted neurogenesis and gliosis due to transgenic overexpression of human soluble IL-1ra in the mouse

Eur J Neurosci. 2008 Feb;27(3):549-58. doi: 10.1111/j.1460-9568.2008.06050.x.

Abstract

Interleukin-1 (IL-1) is one of the most important cytokines in neuroinflammation, in acute conditions as well as during natural ageing and neurodegenerative disorders. Using a transgenic mouse strain with brain-directed overexpression of IL-1 receptor antagonist (Tg hsIL-1ra), we show that blocking IL-1 receptor-mediated activity resulted in abolishing the alterations in neurogenesis in response to acute and chronic neuroinflammation. In addition, using a novel approach to quantifying glial activation, we show that expression of the astrocyte cytoskeletal marker glial fibrillary acidic protein (GFAP) following kainic acid (KA)-induced seizures or during ageing did not change in Tg hsIL-1ra animals. Nevertheless, the astrocyte morphology showed major alterations, consisting of fragmentation of the processes in Tg hsIL-1ra mice. Similarly, although there was a higher degree of basal microglial activation in the transgenic mice than wild-type animals, there was no change following KA-induced seizures or with ageing. Taken together, our results indicate that IL-1 is crucial for the adaptability of the brain to acute and chronic neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / immunology
  • Aging / genetics
  • Aging / immunology
  • Aging / pathology
  • Animals
  • Astrocytes / immunology
  • Astrocytes / metabolism
  • Astrocytes / pathology
  • Cell Proliferation
  • Encephalitis / genetics
  • Encephalitis / immunology*
  • Encephalitis / physiopathology
  • Glial Fibrillary Acidic Protein / metabolism
  • Gliosis / genetics
  • Gliosis / immunology*
  • Gliosis / physiopathology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / antagonists & inhibitors
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / metabolism*
  • Interleukin-1 / metabolism*
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microglia / immunology
  • Microglia / metabolism
  • Microglia / pathology
  • Nerve Regeneration / genetics
  • Nerve Regeneration / immunology*
  • Neuronal Plasticity / genetics
  • Neuronal Plasticity / immunology*
  • Neurons / immunology
  • Neurons / metabolism
  • Seizures / genetics
  • Seizures / immunology
  • Seizures / physiopathology

Substances

  • Glial Fibrillary Acidic Protein
  • Interleukin 1 Receptor Antagonist Protein
  • Interleukin-1