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Blunted neurogenesis and gliosis due to transgenic overexpression of human soluble IL‐1ra in the mouse
Author(s) -
Spulber Stefan,
Oprica Mircea,
Bartfai Tamas,
Winblad Bengt,
Schultzberg Marianne
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06050.x
Subject(s) - neuroinflammation , neurogenesis , gliosis , kainic acid , astrocyte , glial fibrillary acidic protein , genetically modified mouse , transgene , biology , receptor , microbiology and biotechnology , inflammation , neuroscience , endocrinology , immunology , immunohistochemistry , central nervous system , biochemistry , glutamate receptor , gene
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.