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The Journal of Neuroscience, January 15, 2002, 22(2):486-492

Reduced Hippocampal Neurogenesis in Adult Transgenic Mice with Chronic Astrocytic Production of Interleukin-6

Luc Vallières¹, Iain L. Campbell³, Fred H. Gage², and Paul E. Sawchenko¹

Laboratories of ¹ Neuronal Structure and Function and ² Genetics, The Salk Institute for Biological Studies, La Jolla, California 92037, and ³ Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Postnatal neurogenesis can be modulated after brain injury, but the role of the attendant expression of inflammatory mediators in such responses remains to be determined. Here we report that transgenically directed production of interleukin-6 (IL-6) by astroglia decreased overall neurogenesis by 63% in the hippocampal dentate gyrus of young adult transgenic mice. The proliferation, survival, and differentiation of neural progenitor cells labeled with the thymidine analog bromodeoxyuridine were all reduced in the granule cell layer of these mice, whereas their distribution and gliogenesis appeared normal. These effects were not a consequence of general toxicity of the IL-6 transgene, because they were manifested in the absence of neuronal death and of major changes in glial cell number and morphology. These findings suggest that long-term exposure of the brain to proinflammatory mediators such as IL-6, as is seen in certain degenerative disorders and infections, can interfere with adult neurogenesis.

Key words: postnatal neurogenesis; neural progenitor cells; interleukin-6; proinflammatory cytokine; chronic inflammation; hippocampus; transgenic mice; Fluoro-jade

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Copyright © 2002 Society for Neuroscience  0270-6474/02/222486-07$05.00/0

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