Neurotoxicity Research

, Volume 5, Issue 5, pp 339–354

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

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

DOI: 10.1007/BF03033154

Cite this article as:
McPherson, C.A., Kubik, J., Wine, R.N. et al. neurotox res (2003) 5: 339. doi:10.1007/BF03033154

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.

Keywords

Cyclin Trimethyltin Glia Astrocytes Hippocampus Dentate gyrus 

Copyright information

© FP Graham Publishing Co 2003

Authors and Affiliations

  • Christopher A. McPherson
    • 1
  • Julie Kubik
    • 1
  • Robert N. Wine
    • 1
  • Christian Lefebvre D'Hellencourt
    • 1
  • G. Jean Harry
    • 1
  1. 1.Neurotoxicology GroupNational Institute of Environmental Health SciencesResearch Triangle ParkUSA

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