Abstract
Traumatic brain injury (TBI) increases neurogenesis in the forebrain subventricular zone (SVZ) and the hippocampal dentate gyrus (DG). Transforming growth factor-β (TGF-β) superfamily cytokines are important regulators of adult neurogenesis, but their involvement in the regulation of this process after brain injury is unclear. We subjected adult mice to controlled cortical impact (CCI) injury, and isolated RNA from the SVZ and DG at different post-injury time points. qPCR array analysis showed that cortical injury caused significant alterations in the mRNA expression of components and targets of the TGF-β, BMP, and activin signaling pathways in the SVZ and DG after injury, suggesting that these pathways could regulate post-injury neurogenesis. In both neurogenic regions, the injury also induced expression of Runt-related transcription factor-1 (Runx1), which can interact with intracellular TGF-β Smad signaling pathways. CCI injury strongly induced Runx1 expression in activated and proliferating microglial cells throughout the neurogenic regions. Runx1 protein was also expressed in a subset of Nestin- and GFAP-expressing putative neural stem or progenitor cells in the DG and SVZ after injury. In the DG only, these Runx1+ progenitors proliferated. Our data suggest potential roles for Runx1 in the processes of microglial cell activation and proliferation and in neural stem cell proliferation after TBI.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Activins / genetics
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Activins / metabolism
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Animals
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Brain Injuries / genetics*
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Brain Injuries / metabolism
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Brain Injuries / pathology
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Cell Proliferation
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Core Binding Factor Alpha 2 Subunit / genetics*
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Core Binding Factor Alpha 2 Subunit / metabolism
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Dentate Gyrus / cytology
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Dentate Gyrus / injuries
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Dentate Gyrus / metabolism*
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Gene Expression Regulation*
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Glial Fibrillary Acidic Protein
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Intermediate Filament Proteins / genetics
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Intermediate Filament Proteins / metabolism
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Mice
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Microglia / cytology
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Microglia / metabolism
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism
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Nestin
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Neural Stem Cells / cytology
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Neural Stem Cells / metabolism
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Neurogenesis / genetics*
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Neurons / cytology
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Neurons / metabolism
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Prosencephalon / cytology
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Prosencephalon / injuries
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Prosencephalon / metabolism*
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Signal Transduction
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Smad Proteins / genetics
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Smad Proteins / metabolism
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Transforming Growth Factor beta / genetics*
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Transforming Growth Factor beta / metabolism
Substances
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Core Binding Factor Alpha 2 Subunit
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Glial Fibrillary Acidic Protein
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Intermediate Filament Proteins
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Nerve Tissue Proteins
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Nes protein, mouse
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Nestin
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Runx1 protein, mouse
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Smad Proteins
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Transforming Growth Factor beta
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glial fibrillary astrocytic protein, mouse
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Activins
Grants and funding
This project was funded by the Center for Neuroscience and Regenerative Medicine (grant no: 300604 11.0 60855),
http://www.usuhs.mil/cnrm/. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.