Trimethyltin induced hippocampal neurodegeneration elevates cyclins A and B

Autor: Robert N. Wine, G. J. Harry, J. A. Kubik, C. A. McPherson
Rok vydání: 2008
Předmět:
Zdroj: Journal of Neurochemistry. 81:101-105
ISSN: 1471-4159
0022-3042
DOI: 10.1046/j.1471-4159.81.s1.40_17.x
Popis: In certain pathologic states, the response of microglia and associated cytokine production may become spatially and temporally dysregulated contributing to neurodegeneration. Often these responses have been contributed to proliferation of microglia cells. To examine cell cycle related genes and proteins in a model of acute neurodegeneration, the hippocampal toxicant, trimethyltin (TMT; 2.0 mg/kg), was administered to 21 day old CD-1 male mice and the level of cell cycle genes and cellular localization of proteins examined. Neurodegeneration was characterized by neuronal necrosis in the dentate followed by microglia reactivity and activation. mRNA levels for cyclins A2 and B1 were significantly elevated 72 h post-TMT. Western blot analysis indicated minimal increase in whole hippocampal protein levels for cyclin A or B however, immunohistochemical examination of cellular localization demonstrated increased staining for cyclin A primarily in neurons in both the dentate and pyramidal cell layers as early at 24 h post-TMT. Immunohistochemisttry for cyclin B1 showed a peak level of staining at 24 and 48 h in both the dentate and pyramidal cell layers with prominent staining both around the neuronal cell body and in fibrous processes. The staining pattern for each cyclin suggested the involvement of both neurons and microglia. BrdU positive cells were demonstrated predominately in the dentate region and appeared to be primarily neurons with minimal contribution from microglia cells suggesting that the alteration in cell cycle genes is not due to an injury-induced proliferative response of microglia cells in the hippocampus.
Databáze: OpenAIRE
Externí odkaz: