Get access

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

Authors

  • Stefan Spulber,

    1. Department of Neurobiology, Care Sciences and Society, Novum, floor 5, Division of Neurodegeneration and Neuroinflammation, Karolinska Institutet, SE-141 86 Stockholm, Sweden
    Search for more papers by this author
  • Mircea Oprica,

    1. Department of Neurobiology, Care Sciences and Society, Novum, floor 5, Division of Neurodegeneration and Neuroinflammation, Karolinska Institutet, SE-141 86 Stockholm, Sweden
    Search for more papers by this author
  • Tamas Bartfai,

    1. Molecular & Integrative Neurosciences Department, The Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA 92037, USA
    Search for more papers by this author
  • Bengt Winblad,

    1. Department of Neurobiology, Care Sciences and Society, KI – Alzheimer's Disease Research Centre, Karolinska Institutet, SE-14186 Stockholm, Sweden
    Search for more papers by this author
  • Marianne Schultzberg

    1. Department of Neurobiology, Care Sciences and Society, Novum, floor 5, Division of Neurodegeneration and Neuroinflammation, Karolinska Institutet, SE-141 86 Stockholm, Sweden
    Search for more papers by this author

Dr Stefan Spulber, as above.
E-mail: stefan.spulber@ki.se

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.

Ancillary