Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia

Connie Chung, John D. Marson, Quanguang Zhang, Jimok Kim, Wei Hua Wu, Darrell W Brann, Bo Shiun Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity.

Original languageEnglish (US)
Article number37033
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 15 2016

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N-Methyl-D-Aspartate Receptors
Ischemia
Neurons
N-Methylaspartate
Brain Ischemia
Short-Term Memory
Knockout Mice
Hippocampus
Theoretical Models
Calcium
Neuroprotection
Therapeutics

ASJC Scopus subject areas

  • General

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Neuroprotection Mediated through GluN2C-Containing N-methyl-D-aspartate (NMDA) Receptors Following Ischemia. / Chung, Connie; Marson, John D.; Zhang, Quanguang; Kim, Jimok; Wu, Wei Hua; Brann, Darrell W; Chen, Bo Shiun.

In: Scientific Reports, Vol. 6, 37033, 15.11.2016.

Research output: Contribution to journalArticle

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abstract = "Post-ischemic activation of NMDA receptors (NMDARs) has been linked to NMDAR subunit-specific signaling that mediates pro-survival or pro-death activity. Although extensive studies have been performed to characterize the role of GluN2A and GluN2B following ischemia, there is less understanding regarding the regulation of GluN2C. Here, we show that GluN2C expression is increased in acute hippocampal slices in response to ischemia. Strikingly, GluN2C knockout mice, following global cerebral ischemia, exhibit greater neuronal death in the CA1 area of the hippocampus and reduced spatial working memory compared to wild-type mice. Moreover, we find that GluN2C-expressing hippocampal neurons show marked resistance to NMDA-induced toxicity and reduced calcium influx. Using both in vivo and in vitro experimental models of ischemia, we demonstrate a neuroprotective role of GluN2C, suggesting a mechanism by which GluN2C is upregulated to promote neuronal survival following ischemia. These results may provide insights into development of NMDAR subunit-specific therapeutic strategies to protect neurons from excitotoxicity.",
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AU - Brann, Darrell W

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