Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6.
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.
Vallières
Luc
L
Laboratories of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Campbell
Iain L
IL
Gage
Fred H
FH
Sawchenko
Paul E
PE
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001973:Bromodeoxyuridine; D002452:Cell Count; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D005452:Fluoresceins; D005456:Fluorescent Dyes; D015870:Gene Expression; D017930:Genes, Reporter; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology; D009930:Organic Chemicals; D010641:Phenotype; D019076:Transgenes
D005452:Fluoresceins; D005456:Fluorescent Dyes; D015850:Interleukin-6; D009930:Organic Chemicals; C435731:fluoro jade; D001973:Bromodeoxyuridine