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Am J Pathol. 1999 Sep;155(3):995-1004.

Potentiation of excitotoxicity in transgenic mice overexpressing neuronal cyclooxygenase-2.

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  • 1Neuroinflammation Research Laboratories, Department of Psychiatry, Brookdale Center for Developmental and Molecular Biology, Mount Sinai School of Medicine, New York, New York, USA.

Abstract

In this study we describe the generation of a transgenic mouse model with neuronal overexpression of the human cyclooxygenase-2, h(COX)-2, to explore its role in excitotoxicity. We report that overexpression of neuronal hCOX-2 potentiates the intensity and lethality of kainic acid excitotoxicity in coincidence with potentiation of expression of the immediate early genes c-fos and zif-268. In vitro studies extended the in vivo findings and revealed that glutamate excitotoxicity is potentiated in primary cortico-hippocampal neurons derived from hCOX-2 transgenic mice, possibly through potentiation of mitochondrial impairment. This study is the first to demonstrate a cause-effect relationship between neuronal COX-2 expression and excitotoxicity. This model system will allow the systematic examination of the role of COX-2 in mechanisms of neurodegeneration that involve excitatory amino acid pathways.

PMID:
10487857
[PubMed - indexed for MEDLINE]
PMCID:
PMC1866889
Free PMC Article
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