Serine racemase deletion protects against cerebral ischemia and excitotoxicity

AK Mustafa, AS Ahmad, E Zeynalov… - Journal of …, 2010 - Soc Neuroscience
AK Mustafa, AS Ahmad, E Zeynalov, SK Gazi, G Sikka, JT Ehmsen, RK Barrow, JT Coyle
Journal of Neuroscience, 2010Soc Neuroscience
d-Serine, formed from l-serine by serine racemase (SR), is a physiologic 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 …
d-Serine, formed from l-serine by serine racemase (SR), is a physiologic 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.
Soc Neuroscience