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Potential signalling pathways underlying corticotrophin-releasing hormone-mediated neuroprotection from excitotoxicity in rat hippocampus
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UNSPECIFIED (2002) Potential signalling pathways underlying corticotrophin-releasing hormone-mediated neuroprotection from excitotoxicity in rat hippocampus. JOURNAL OF NEUROCHEMISTRY, 80 (3). pp. 416-425. ISSN 0022-3042.
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Abstract
In several neurological disorders including cerebral ischaemia, glutamate has been implicated as a neurotoxic agent in the mechanisms leading to neuronal cell death. The role of corticotrophin-releasing hormone (CRH), the 41-amino acid peptide, which activates the HPA axis in response to stressful stimuli, remains controversial. In this study, we report that CRH in low physiological concentrations (2 pm), prevented glutamate-induced neurotoxicity via receptor-mediated mechanisms when administered to organotypic hippocampal cultures both during and after the glutamate-induced insult. Detailed investigations on the mechanisms mediating this neuroprotective effect showed that activation of the adenylate cyclase pathway and induction of MAP kinase phosphorylation mediate the CRH action. In addition we showed that CRH can inhibit the phosphorylation of JNK/SAPK by glutamate. Most importantly, we showed that CRH can afford neuroprotection against neurotoxicity up to 12 h following the insult, suggesting that CRH is acting at a late stage in the neuronal death cycle, and this might be important in the development of novel neuroprotective agents in order to improve neuronal survival following the insult.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QD Chemistry R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry |
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| Journal or Publication Title: | JOURNAL OF NEUROCHEMISTRY | ||||
| Publisher: | BLACKWELL PUBLISHING LTD | ||||
| ISSN: | 0022-3042 | ||||
| Official Date: | February 2002 | ||||
| Dates: |
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| Volume: | 80 | ||||
| Number: | 3 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 416-425 | ||||
| Publication Status: | Published |
Data sourced from Thomson Reuters' Web of Knowledge
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