Endogenous interferon gamma directly regulates neural precursors in the non-inflammatory brain

Li, Li, Walker, Tara L., Zhang, Ying, Mackay, Eirinn W. and Bartlett, Perry F. (2010) Endogenous interferon gamma directly regulates neural precursors in the non-inflammatory brain. Journal of Neuroscience, 30 27: 9038-9050. doi:10.1523/JNEUROSCI.5691-09.2010

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Author Li, Li
Walker, Tara L.
Zhang, Ying
Mackay, Eirinn W.
Bartlett, Perry F.
Title Endogenous interferon gamma directly regulates neural precursors in the non-inflammatory brain
Formatted title
Endogenous interferon γ directly regulates neural precursors in the non-inflammatory brain
Journal name Journal of Neuroscience   Check publisher's open access policy
ISSN 0270-6474
Publication date 2010-07-07
Sub-type Article (original research)
DOI 10.1523/JNEUROSCI.5691-09.2010
Open Access Status File (Publisher version)
Volume 30
Issue 27
Start page 9038
End page 9050
Total pages 13
Editor John H. R. Maunsell
Place of publication New York, NY, U.S.A.
Publisher Society for Neuroscience
Collection year 2011
Language eng
Formatted abstract
Although a number of growth factors have been shown to be involved in neurogenesis, the role of inflammatory cytokines remains relatively unexplored in the normal brain. Here we investigated the effect of interferon gamma (IFNγ) in the regulation of neural precursor (NP) activity in both the developing and the adult mouse brain. Exogenous IFNγ inhibited neurosphere formation from the wild-type neonatal and adult subventricular zone (SVZ). More importantly, however, these effects were mirrored in vivo, with mutant mice lacking endogenous IFNγ displaying enhanced neurogenesis, as demonstrated by an increase in proliferative bromodeoxyuridine-labeled cells in the SVZ and an increased percentage of newborn neurons in the olfactory bulb. Furthermore, NPs isolated from IFNγ null mice exhibited an increase in self-renewal ability and in the capacity to produce differentiated neurons and oligodendrocytes. These effects resulted from the direct action of IFNγ on the NPs, as determined by single-cell assays and the fact that nearly all the neurospheres were derived from cells positive for major histocompatibility complex class I antigen, a downstream marker of IFNγ-mediated activation. Moreover, the inhibitory effect was ameliorated in the presence of SVZ-derived microglia, with their removal resulting in almost complete inhibition of NP proliferation. Interestingly, in contrast to the results obtained in the adult, exogenous IFNγ treatment stimulated neurosphere formation from the embryonic brain, an effect that was mediated by sonic hedgehog. Together these findings provide the first direct evidence that IFNγ acts as a regulator of the active NP pool in the non-inflammatory brain.
Copyright © 2010 the authors.
Keyword Central-nervous-system
Cell-cycle arrest
Adult-mouse brain
Sonic hedgehog
Hippocampal neurogenesis
Neuronal differentiation
Progenitor proliferation
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
Queensland Brain Institute Publications
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Citation counts: TR Web of Science Citation Count  Cited 31 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 36 times in Scopus Article | Citations
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Created: Sun, 25 Jul 2010, 00:05:06 EST