Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways.
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| Title: | Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. |
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| Authors: | Hardingham, Giles E., Fukunaga, Yuko, Bading, Hilmar |
| Source: | Nature Neuroscience. May2002, Vol. 5 Issue 5, p405. 10p. |
| Subjects: | Methyl aspartate, Cyclic adenylic acid, Gene expression |
| Abstract: | Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene expression as strongly as did stimulation of L-type calcium channels. In contrast, calcium entry through extrasynaptic NMDA receptors, triggered by bath glutamate exposure or hypoxic/ischemic conditions, activated a general and dominant CREB shut-off pathway that blocked induction of BDNF expression. Synaptic NMDA receptors have anti-apoptotic activity, whereas stimulation of extrasynaptic NMDA receptors caused loss of mitochondrial membrane potential (an early marker for glutamate-induced neuronal damage) and cell death. Specific blockade of extrasynaptic NMDA receptors may effectively prevent neuron loss following stroke and other neuropathological conditions associated with glutamate toxicity. [ABSTRACT FROM AUTHOR] |
| Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
| FullText | Links: – Type: pdflink Text: Availability: 0 |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 9511831 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Hardingham%2C+Giles+E%2E%22">Hardingham, Giles E.</searchLink><br /><searchLink fieldCode="AR" term="%22Fukunaga%2C+Yuko%22">Fukunaga, Yuko</searchLink><br /><searchLink fieldCode="AR" term="%22Bading%2C+Hilmar%22">Bading, Hilmar</searchLink> – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Nature+Neuroscience%22">Nature Neuroscience</searchLink>. May2002, Vol. 5 Issue 5, p405. 10p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Methyl+aspartate%22">Methyl aspartate</searchLink><br /><searchLink fieldCode="DE" term="%22Cyclic+adenylic+acid%22">Cyclic adenylic acid</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+expression%22">Gene expression</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Here we report that synaptic and extrasynaptic NMDA (N-methyl-D-aspartate) receptors have opposite effects on CREB (cAMP response element binding protein) function, gene regulation and neuron survival. Calcium entry through synaptic NMDA receptors induced CREB activity and brain-derived neurotrophic factor (BDNF) gene expression as strongly as did stimulation of L-type calcium channels. In contrast, calcium entry through extrasynaptic NMDA receptors, triggered by bath glutamate exposure or hypoxic/ischemic conditions, activated a general and dominant CREB shut-off pathway that blocked induction of BDNF expression. Synaptic NMDA receptors have anti-apoptotic activity, whereas stimulation of extrasynaptic NMDA receptors caused loss of mitochondrial membrane potential (an early marker for glutamate-induced neuronal damage) and cell death. Specific blockade of extrasynaptic NMDA receptors may effectively prevent neuron loss following stroke and other neuropathological conditions associated with glutamate toxicity. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Nature Neuroscience is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1038/nn835 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 10 StartPage: 405 Subjects: – SubjectFull: Methyl aspartate Type: general – SubjectFull: Cyclic adenylic acid Type: general – SubjectFull: Gene expression Type: general Titles: – TitleFull: Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Hardingham, Giles E. – PersonEntity: Name: NameFull: Fukunaga, Yuko – PersonEntity: Name: NameFull: Bading, Hilmar IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2002 Type: published Y: 2002 Identifiers: – Type: issn-print Value: 10976256 Numbering: – Type: volume Value: 5 – Type: issue Value: 5 Titles: – TitleFull: Nature Neuroscience Type: main |
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