Cellular origin and regulation of D- and L-serine in in vitro and in vivo models of cerebral ischemia

Takato Abe, Masataka Suzuki, Jumpei Sasabe, Shinichi Takahashi, Miyuki Unekawa, Kyoko Mashima, Takuya Iizumi, Kenji Hamase, Ryuichi Konno, Sadakazu Aiso, Norihiro Suzuki

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 synthesizes D-serine from L-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 for D-/L-serine remain elusive. The D-/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 that D-serine is derived from neurons, while L-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 synthesizes L-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 in D-/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.

Original languageEnglish
Pages (from-to)1928-1935
Number of pages8
JournalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
Volume34
Issue number12
DOIs
Publication statusPublished - 2014 Dec 1

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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