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Injury-Induced Neurogenesis: Consideration of Resident Microglia as Supportive of Neural Progenitor Cells

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Abstract

The induction of neurogenesis in the adult subgranular zone (SGZ) by injury is often accompanied by changes in the extracellular environment that can have significant impacts on neural progenitor cells (NPCs). We examined the induction of neurogenesis in the SGZ at 72 h following an injection of the hippocampal toxicant, trimethyltin (TMT; 2 mg/kg, ip) inducing apoptosis in dentate granule neurons. BrdU+ incorporation during the active period of neuronal death indicated NPC proliferation and migration of newly generated cells into the granule cell layer (GCL). BrdU+ cells were transiently in contact with process bearing microglia within the inner SGZ layer. Contact with GFAP+ astrocyte processes occurred once cells were within the GCL. A small percentage of the BrdU+ cells within the SGZ region showed immunoreactivity for tumor necrosis factor (TNF) p75 receptor (TNFp75R). In mice deficient for TNFp75R, TMT injection produced an equivalent level of dentate granule cell death however; BrdU+ cells were localized at the SGZ as compared to the presence of cells within the GCL in the WT mice dosed with TMT. These data suggest that cells generated by NPCs in the SGZ induced with a focal lesion to the dentate granule neurons of adolescent mice maintain the capacity to utilize the neuroinflammation and microglia responses within their environment for migration into the GCL.

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Acknowledgments

This study was supported by the division of intramural research of the National Institute of Environmental Health Science, National Institutes of Health, and Department of Health and Human Services. The authors wish to thank Drs Mary Gilbert and Susan McGuire for their review of the manuscript, and Mr. Robert Wine for technical expertise.

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  1. Neurotoxicology Group, Laboratory of Molecular Toxicology, National Institute of Environmental Health Science, National Institutes of Health, MD C1-04, P.O. Box 12233, Research Triangle Park, NC, 27709, USA

    Christopher A. McPherson, Andrew D. Kraft & G. Jean Harry

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  1. Christopher A. McPherson
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  2. Andrew D. Kraft
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  3. G. Jean Harry
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Correspondence to G. Jean Harry.

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McPherson, C.A., Kraft, A.D. & Harry, G.J. Injury-Induced Neurogenesis: Consideration of Resident Microglia as Supportive of Neural Progenitor Cells. Neurotox Res 19, 341–352 (2011). https://doi.org/10.1007/s12640-010-9199-6

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  • DOI: https://doi.org/10.1007/s12640-010-9199-6

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