TLR2 activation inhibits embryonic neural progenitor cell proliferation

Okun, Eitan, Griffioen, Kathleen J., Son, Tae Gen, Lee, Jong-Hwan, Roberts, Nicholas J., Mughal, Mohamed R., Hutchison, Emmette, Cheng, Aiwu, Arumugam, Thiruma V., Lathia, Justin D., van Praag, Henriette and Mattson, Mark P. (2010) TLR2 activation inhibits embryonic neural progenitor cell proliferation. Journal of Neurochemistry, 114 2: 462-474. doi:10.1111/j.1471-4159.2010.06778.x

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Author Okun, Eitan
Griffioen, Kathleen J.
Son, Tae Gen
Lee, Jong-Hwan
Roberts, Nicholas J.
Mughal, Mohamed R.
Hutchison, Emmette
Cheng, Aiwu
Arumugam, Thiruma V.
Lathia, Justin D.
van Praag, Henriette
Mattson, Mark P.
Title TLR2 activation inhibits embryonic neural progenitor cell proliferation
Journal name Journal of Neurochemistry   Check publisher's open access policy
ISSN 0022-3042
Publication date 2010-07
Year available 2010
Sub-type Article (original research)
DOI 10.1111/j.1471-4159.2010.06778.x
Volume 114
Issue 2
Start page 462
End page 474
Total pages 13
Editor Sean Murphy
Tony J Turner
Place of publication United Kingdom
Publisher Wiley-Blackwell Publishing Ltd.
Collection year 2011
Language eng
Subject C1
920111 Nervous System and Disorders
060105 Cell Neurochemistry
1109 Neurosciences
Abstract Toll-like receptors (TLRs) play essential roles in innate immunity, and increasing evidence indicates that these receptors are expressed in neurons, astrocytes, and microglia in the brain, where they mediate responses to infection, stress, and injury. To address the possibility that TLR2 heterodimer activation could affect progenitor cells in the developing brain, we analyzed the expression of TLR2 throughout mouse cortical development, and assessed the role of TLR2 heterodimer activation in neuronal progenitor cell (NPC) proliferation. TLR2 mRNA and protein was expressed in the cortex in embryonic and early postnatal stages of development, and in cultured cortical NPC. While NPC from TLR2-deficient and wild type embryos had the same proliferative capacity, TLR2 activation by the synthetic bacterial lipopeptides Pam(3)CSK(4) and FSL1, or low molecular weight hyaluronan, an endogenous ligand for TLR2, inhibited neurosphere formation in vitro. Intracerebral in utero administration of TLR2 ligands resulted in ventricular dysgenesis characterized by increased ventricle size, reduced proliferative area around the ventricles, increased cell density, an increase in phospho-histone 3 cells, and a decrease in BrdU+ cells in the sub-ventricular zone. Our findings indicate that loss of TLR2 does not result in defects in cerebral development. However, TLR2 is expressed and functional in the developing telencephalon from early embryonic stages and infectious agent-related activation of TLR2 inhibits NPC proliferation. TLR2-mediated inhibition of NPC proliferation may therefore be a mechanism by which infection, ischemia, and inflammation adversely affect brain development.
Keyword Toll-like Receptors
Cerebral cortex
Neuronal progenitor cells
Nuclear Factor-kappa B
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Official 2011 Collection
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Citation counts: TR Web of Science Citation Count  Cited 35 times in Thomson Reuters Web of Science Article | Citations
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Created: Sun, 11 Jul 2010, 00:03:35 EST