Excitotoxic stimulation activates distinct pathogenic and protective expression signatures in the hippocampus.

Excitotoxic events underlying ischaemic and traumatic brain injuries activate degenerative and protective pathways, particularly in the hippocampus. To understand opposing pathways that determine the brain's response to excitotoxicity, we used hippocampal explants, thereby eliminating systemic variables during a precise protocol of excitatory stimulation. N-methyl-d-aspartate (NMDA) was applied for 20 min and total RNA isolated one and 24 h later for neurobiology-specific microarrays.

Genomic approaches for investigating mechanisms of genotoxicity.

The current genetic toxicity testing battery enables an accurate and effective detection of genotoxicity associated with exposure to chemicals. However, the interpretation of the data in light of the relevant risk to humans is often difficult due to limited insight into underlying genotoxic mechanisms. Thus, the development of experimental approaches capable of differentiating genotoxic mechanisms is expected to facilitate risk assessment.

Gene expression profile analysis: an emerging approach to investigate mechanisms of genotoxicity.

The response to stress triggers transcriptional activation of genes involved in cell survival and/or cell death. Thus, the monitoring of gene expression levels in large gene sets or whole genomes in response to various agents (toxicogenomics) has been proposed as a tool for investigating mechanisms of toxicity. Although standard in vitro genetic toxicity testing provides relatively simple and accurate hazard detection, interpretation of positive findings, i.

Differentiating mechanisms of toxicity using global gene expression analysis in Saccharomyces cerevisiae.

Genotoxic stress triggers a variety of biological responses including the transcriptional activation of genes regulating DNA repair, cell survival and cell death. Genomic approaches, which monitor gene expressions across large numbers of genes, can serve as a powerful tool for exploring mechanisms of toxicity. Here, using five different agents, we investigated whether the analysis of genome-wide expression profiles in Saccharomyces cerevisiae could provide insights into mechanisms of genotoxicity versus cytotoxicity.

Biphasic NF-kappaB activation in the excitotoxic hippocampus.

Excitotoxic stimulation of NMDA receptors results in the activation of a variety of cellular responses. The inducible transcription factor NF-kappaB is known to be involved in excitotoxic responses by neurons. Here, we show that NF-kappaB activation occurs in a biphasic manner in hippocampal slices following a 20-min N-methyl- d-aspartate (NMDA) exposure.