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

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...

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Published in:	Neurotoxicity research Vol. 5; no. 5; pp. 339 - 354
Main Authors:	McPherson, Christopher A, Kubik, Julie, Wine, Robert N, D'Hellencourt, Christian Lefebvre, Harry, G Jean
Format:	Journal Article
Language:	English
Published:	United States Springer Verlag 2003
Subjects:	Animals Astrocytes - drug effects Astrocytes - metabolism Astrocytes - pathology Cell Division - drug effects Cyclin A - biosynthesis Cyclin A - metabolism Cyclin B - biosynthesis Cyclin B - metabolism Cyclin D1 - biosynthesis Cyclin D1 - metabolism Dentate Gyrus - drug effects Dentate Gyrus - metabolism Fluorescent Antibody Technique Hippocampus - drug effects Hippocampus - metabolism Hippocampus - pathology Human health and pathology In Situ Hybridization Life Sciences Male Mice Nerve Tissue Proteins - biosynthesis Neuroglia - drug effects Neuroglia - metabolism Neuroglia - pathology Nuclease Protection Assays RNA, Messenger - biosynthesis Trimethyltin Compounds - toxicity Tumor Necrosis Factor-alpha - biosynthesis Astrocytes Cyclin gyrus Glia Trimethyltin Hippocampus Dentate
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Summary:	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 hrs. Neuronal necrosis and microglia differentiation to a phagocytic phenotype is temporally correlated with peak elevations in TNF-alpha, cyclin A2, cyclin B1 and cyclin D1 at 72 h post-TMT. TNF-alpha 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1029-8428 1476-3524
DOI:	10.1007/bf03033154