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Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage

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Abstract

The interactions of glia and neurons during injury and subsequent neurodegeneration are a subject of interest both in disease and chemical-induced brain injury. One such model is the prototypical hippocampal toxicant trimethyltin (TMT). An acute injection of TMT (2.0 mg/kg, i.p.) to postnatal day 21 CD-1 male mice produced neuronal necrosis and loss of dentate granule cells, astrocyte hypertrophy, and microglia activation in the hippocampus within 24 h. Neuronal necrosis and microglia differentiation to a phagocytic phenotype is temporally correlated with peak elevations in TNF-α, cyclin A2, cyclin B1 and cyclin D1 at 72 h post-TMT. TNF-α mRNA levels were significantly elevated in the hippocampus by 12 h and remained elevated for 72 h. mRNA levels for cyclin A2 and cyclin B1 were elevated by approximately 2-fold at 72 h. Immunohistochemistry suggested a cellular localization of cyclin A to microglia in the region of neuronal necrosis in the dentate, cyclin B in glial cells in juxtaposition to neurons in the hilus of the hippocampus and cyclin D1 to non-glial cells in the dentate. mRNA levels for cyclin D1 were elevated approximately 1.5-fold by 72 h as determined by RNase protection assay. No changes were seen in mRNA levels for cyclins E, F, G1, G2, H or I nor cyclin dependent kinases. These elevations are not associated with proliferation of microglia as determined by BrdU incorporation and Ki-67 immunohistochemistry. Upregulation of cell cycle genes was associated with cellular processes other than proliferation and may contribute to the differentiation of microglia to a phagocytic phenotype. These data suggest an integrated role for cell cycle regulation of neural cells in the manifestation of hippocampal pathophysiology.

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  1. Neurotoxicology Group, National Institute of Environmental Health Sciences, 27709, Research Triangle Park, NC, USA

    Christopher A. McPherson, Julie Kubik, Robert N. Wine, Christian Lefebvre D'Hellencourt & G. Jean Harry

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  1. Christopher A. McPherson
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  2. Julie Kubik
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McPherson, C.A., Kubik, J., Wine, R.N. et al. Alterations in cyclin A, B, and D1 in mouse dentate gyrus following TMT-induced hippocampal damage. neurotox res 5, 339–354 (2003). https://doi.org/10.1007/BF03033154

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