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Endoplasmic Reticulum Stress Inhibition Protects against Excitotoxic Neuronal Injury in the Rat Brain
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2007 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 27, no 4, 901-908 p.Article in journal (Refereed) Published
Abstract [en]

Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2α (eukaryotic translation initiation factor 2 subunit α) dephosphorylation, significantly reduced KA-induced ERstress and neuronal death in vivo and in vitro. KA-induced rise in intracellular calcium was not affected by Salubrinal. The results show that ER responses are essential parts of excitotoxicity mediated by glutamate receptor activation and that Salubrinal decreases neuronal death in vivo. Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders.

Place, publisher, year, edition, pages
2007. Vol. 27, no 4, 901-908 p.
Keyword [en]
kainic acid, hippocampus, salubrinal, PERK, eIF2{alpha}, caspase-12
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-23434DOI: 10.1523/JNEUROSCI.4289-06.2007ISI: 000243725200023PubMedID: 17251432OAI: oai:DiVA.org:uu-23434DiVA: diva2:51208
Available from: 2007-01-29 Created: 2007-01-29 Last updated: 2011-04-07Bibliographically approved

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Lindholm, DanKorhonen, Laura
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