期刊
EUROPEAN JOURNAL OF NEUROSCIENCE
卷 27, 期 3, 页码 549-558出版社
BLACKWELL PUBLISHING
DOI: 10.1111/j.1460-9568.2008.06050.x
关键词
ageing; dentate gyrus; interleukin-1; kainic acid; neurogenesis; neuroinflammation
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.
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