RGD Reference Report - Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors. - Rat Genome Database

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Hypoxic/ischemic conditions induce expression of the putative pro-death gene Clca1 via activation of extrasynaptic N-methyl-D-aspartate receptors.

Authors: Wahl, AS  Buchthal, B  Rode, F  Bomholt, SF  Freitag, HE  Hardingham, GE  Ronn, LC  Bading, H 
Citation: Wahl AS, etal., Neuroscience. 2009 Jan 12;158(1):344-52. Epub 2008 Jun 14.
RGD ID: 4188872
Pubmed: PMID:18616988   (View Abstract at PubMed)
DOI: DOI:10.1016/j.neuroscience.2008.06.018   (Journal Full-text)

The stimulation of extrasynaptic N-methyl-D-aspartate (NMDA) receptors triggers cell death pathways and has been suggested to play a key role in cell degeneration and neuron loss associated with glutamate-induced excitotoxicity. In contrast, synaptic NMDA receptors promote neuronal survival. One mechanism through which extrasynaptic NMDA receptors damage neurons may involve Clca1, which encodes a putative calcium-activated chloride channel. Here we show that Clca1 expression is induced in cultured rat hippocampal neurons exposed to oxygen/glucose-free media; this induction is mediated by a signaling pathway activated by extrasynaptic NMDA receptors. Clca1 mRNA levels also increased in the gerbil hippocampus following a transient forebrain ischemia caused by bilateral carotid occlusion. Microelectrode array recordings revealed that oxygen-glucose deprivation enhances hippocampal network firing rates, which induces c-fos transcription through a signaling pathway that, in contrast to Clca1, is activated by synaptic but not extrasynaptic NMDA receptors. Thus, conditions of low oxygen/glucose lead to the activation of both extrasynaptic and synaptic NMDA receptors that regulate distinct target genes. Clca1 may be part of the genomic death program triggered by extrasynaptic NMDA receptors; it could be a marker for ischemic brain damage and a possible target for therapeutic interventions.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to hypoxia  IEP 4188872 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
zymogen granule membrane  IDA 4188872 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Clca1  (chloride channel accessory 1)


Additional Information