title: Cellular origin and regulation of D- and L-serine in in vitro and in vivo models of cerebral ischemia.
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.
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takato
authors.initials: T
authors.lastname: Abe
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Suzuki
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Jumpei
authors.initials: J
authors.lastname: Sasabe
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Miyuki
authors.initials: M
authors.lastname: Unekawa
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Mashima
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Iizumi
authors.affiliation: Graduate School of Pharmaceutical Sciences Kyushu University, Higashi-ku, Fukuoka, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hamase
authors.affiliation: Department of Pharmacological Sciences, International University of Health and Welfare, Ohtawara, Tochigi, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Konno
authors.affiliation: Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Sadakazu
authors.initials: S
authors.lastname: Aiso
authors.affiliation: Department of Neurology, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D050543:Phosphoglycerate Dehydrogenase / Q000378:metabolism; D011247:Pregnancy; D061251:Primary Cell Culture; D019998:Racemases and Epimerases / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000378:metabolism*; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D012694:Serine; D050543:Phosphoglycerate Dehydrogenase; D019998:Racemases and Epimerases