Cellular Origin and Regulation of D-and L-Serine in in Vitro and in Vivo Models of Cerebral Ischemia. Issue 12 (December 2014)

• Record Type: Journal Article
• Authors: Abe, Takato; Suzuki, Masataka; Sasabe, Jumpei; Takahashi, Shinichi; Unekawa, Miyuki; Mashima, Kyoko; Iizumi, Takuya; Hamase, Kenji; Konno, Ryuichi; Aiso, Sadakazu; Suzuki, Norihiro
• Is Part Of: Journal of cerebral blood flow & metabolism. Volume 34:Issue 12(2014)
• Page Start: 1928
• Page End: 1935
• Publication Date: 2014-12
• Subjects: excitotoxicity -- focal ischemia -- glial cells -- glutamate -- neuronal-glial interaction; Cerebral circulation -- Periodicals; Brain -- Metabolism -- Periodicals; Brain -- Blood-vessels -- Periodicals; Cerebrovascular disease -- Periodicals; 612.824
• DOI: 10.1038/jcbfm.2014.164
• Languages: English
• ISSNs: 0271-678X

Abstract

D -Serine is known to be essential for the activation of the N -methyl-D -aspartate (NMDA) receptor in the excitation of glutamatergic neurons, which have critical roles in long-term potentiation and memory formation.D -Serine is also thought to be involved in NMDA receptor-mediated neurotoxicity. The deletion of serine racemase (SRR), which synthesizesD -Serine fromL -Serine, was recently reported to improve ischemic damage in mouse middle cerebral artery occlusion model. However, the cell type in which this phenomenon originates and the regulatory mechanism forD -/L -Serine remain elusive. TheD -/L -Serine content in ischemic brain increased until 20 hours after recanalization and then leveled off gradually. The results of in vitro experiments using cultured cells suggested thatD -Serine is derived from neurons, whileL -Serine seems to be released from astroglia. Immunohistochemistry studies of brain tissue after cerebral ischemia showed that SRR is expressed in neurons, and 3-phosphoglycerate dehydrogenase (3-PGDH), which synthesizesL -Serine from 3-phosphoglycerate, is located in astrocytes, supporting the results of the in vitro experiments. A western blot analysis showed that neither SRR nor 3-PGDH was upregulated after cerebral ischemia. Therefore, the increase inD -/L -Serine was not related to an increase in SRR or 3-PGDH, but to an increase in the substrates of SRR and 3-PGDH.