Serine racemase deletion protects against cerebral ischemia and excitotoxicity

Asif K. Mustafa; Abdullah S. Ahmad; Emil Zeynalov; Sadia K. Gazi; Gautam Sikka; Jeffrey T. Ehmsen; Roxanne K. Barrow; Joseph T. Coyle; Solomon H. Snyder; Sylvain Doré

doi:10.1523/JNEUROSCI.4297-09.2010

Serine racemase deletion protects against cerebral ischemia and excitotoxicity

Asif K. Mustafa, Abdullah S. Ahmad, Emil Zeynalov, Sadia K. Gazi, Gautam Sikka, Jeffrey T. Ehmsen, Roxanne K. Barrow, Joseph T. Coyle, Solomon H. Snyder, Sylvain Doré

School of Medicine

Research output: Contribution to journal › Article › peer-review

80 Scopus citations

Abstract

D-Serine, formed from L-serine by serine racemase (SR), is a physilologic coagonist at NMDA receptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine in NMDA receptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR knock-out mice, NO formation and nitrosylation of NO targets are substantially reduced. Infarct volume following middle cerebral artery occlusion is dramatically diminished in several regions of the brains of SR mutant mice despite evidence of increased NMDA receptor number and sensitivity.

Original language	English (US)
Pages (from-to)	1413-1416
Number of pages	4
Journal	Journal of Neuroscience
Volume	30
Issue number	4
DOIs	https://doi.org/10.1523/JNEUROSCI.4297-09.2010
State	Published - Jan 27 2010

ASJC Scopus subject areas

General Neuroscience

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10.1523/JNEUROSCI.4297-09.2010

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title = "Serine racemase deletion protects against cerebral ischemia and excitotoxicity",

abstract = "D-Serine, formed from L-serine by serine racemase (SR), is a physilologic coagonist at NMDA receptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine in NMDA receptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR knock-out mice, NO formation and nitrosylation of NO targets are substantially reduced. Infarct volume following middle cerebral artery occlusion is dramatically diminished in several regions of the brains of SR mutant mice despite evidence of increased NMDA receptor number and sensitivity.",

author = "Mustafa, {Asif K.} and Ahmad, {Abdullah S.} and Emil Zeynalov and Gazi, {Sadia K.} and Gautam Sikka and Ehmsen, {Jeffrey T.} and Barrow, {Roxanne K.} and Coyle, {Joseph T.} and Snyder, {Solomon H.} and Sylvain Dor{\'e}",

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doi = "10.1523/JNEUROSCI.4297-09.2010",

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TY - JOUR

T1 - Serine racemase deletion protects against cerebral ischemia and excitotoxicity

AU - Mustafa, Asif K.

AU - Ahmad, Abdullah S.

AU - Zeynalov, Emil

AU - Gazi, Sadia K.

AU - Sikka, Gautam

AU - Ehmsen, Jeffrey T.

AU - Barrow, Roxanne K.

AU - Coyle, Joseph T.

AU - Snyder, Solomon H.

AU - Doré, Sylvain

PY - 2010/1/27

Y1 - 2010/1/27

N2 - D-Serine, formed from L-serine by serine racemase (SR), is a physilologic coagonist at NMDA receptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine in NMDA receptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR knock-out mice, NO formation and nitrosylation of NO targets are substantially reduced. Infarct volume following middle cerebral artery occlusion is dramatically diminished in several regions of the brains of SR mutant mice despite evidence of increased NMDA receptor number and sensitivity.

AB - D-Serine, formed from L-serine by serine racemase (SR), is a physilologic coagonist at NMDA receptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine in NMDA receptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR knock-out mice, NO formation and nitrosylation of NO targets are substantially reduced. Infarct volume following middle cerebral artery occlusion is dramatically diminished in several regions of the brains of SR mutant mice despite evidence of increased NMDA receptor number and sensitivity.

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Serine racemase deletion protects against cerebral ischemia and excitotoxicity

Abstract

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