Journal
NEUROSCIENCE LETTERS
Volume 380, Issue 3, Pages 229-233Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2005.01.055
Keywords
geldanamycin; Hsp70; ischemia; hippocampal organotypic cultures; protein aggregation
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Funding
- NIGMS NIH HHS [GM 49831] Funding Source: Medline
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Our prior work demonstrated that geldanamycin (GA) reduced injury due to oxygen-glucose deprivation (OGD) in primary astrocyte cultures. Using medium with an ionic composition similar to that observed during in vivo global ischemia, the selectivity and temporal profile of CA1 neuronal damage seen in vivo was mimicked with OGD in mouse hippocampal organotypic slice cultures. The present study tested the ability of GA to reduce delayed neuronal death in such cultures. Treating organotypic cultures with 100 nM GA for 24 h prior to OGD induced Hsp70 and significantly reduced CA1 neuronal damage. Staining with ubiquitin to identify protein aggregates revealed reduced redistribution of ubiquitin, consistent with reduced protein aggregation likely due at least in part to induction of Hsp70 by GA. (c) 2005 Elsevier Ireland Ltd. All rights reserved.
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