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PMID: 11784794 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Reduced hippocampal neurogenesis in adult transgenic mice with chronic astrocytic production of interleukin-6.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 22 ·No. 2 ·2002-01-15 ·Pages 486-92

Vallières L, Campbell IL, Gage FH, Sawchenko PE

Abstract

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.

MeSH Terms
Animals Astrocytes/cytology,metabolism Bromodeoxyuridine Cell Count Cell Differentiation/genetics Cell Division/genetics Cell Survival/genetics Dentate Gyrus/cytology,metabolism Fluoresceins Fluorescent Dyes Gene Expression Genes, Reporter Hippocampus/cytology,metabolism Immunohistochemistry Interleukin-6/biosynthesis,genetics Mice Mice, Transgenic Neurons/cytology Organic Chemicals Phenotype Transgenes
Chemicals
Fluoresceins Fluorescent Dyes Interleukin-6 Organic Chemicals fluoro jade Bromodeoxyuridine
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Vallières Luc
Laboratories of Neuronal Structure and Function, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
Campbell Iain L
Gage Fred H
Sawchenko Paul E
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2002-01-15
Pages
486-92
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6758670
Subset
IM
Grants
NINDS NIH HHS · NS21182 · United States
NIA NIH HHS · AGO6088 · United States
NIA NIH HHS · AGO5131 · United States
NINDS NIH HHS · R37 NS021182 · United States
NIMH NIH HHS · MH50426 · United States
NINDS NIH HHS · R01 NS021182 · United States
External Links
PubMed source PMC Full Text View journal details
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