Modulation of d-Serine Levels in Brains of Mice Lacking PICK1

Takatoshi Hikida, Asif K. Mustafa, Kazuhisa Maeda, Kumiko Fujii, Roxanne K. Barrow, Masoumeh Saleh, Richard L. Huganir, Solomon H. Snyder, Kenji Hashimoto, Akira Sawa

Research output: Contribution to journalArticlepeer-review

Abstract

Background: d-serine is an endogenous coagonist of the N-methyl-d-aspartate subtype glutamate receptor. Genetic association studies have implicated genes coding for enzymes associated with d-serine metabolism in schizophrenia and bipolar disorder. Methods: Protein expression of serine racemase (SR) and its binding partner, protein interacting with C-kinase (PICK1), were examined by Western blotting in brains from wildtype and PICK1 knockout mice. Levels of d-serine in wildtype and PICK1 mice were also examined by an established high-pressure liquid chromatography protocol. Results: Expression of SR and PICK1 proteins was developmentally regulated. Although no change was observed in the level of SR protein, levels of d-serine were selectively decreased in the forebrain of neonatal PICK1 knockout mice, compared with those in wildtype mice. Conclusions: PICK1 may be involved in the regulation of brain d-serine levels and SR in a spatially and temporally specific manner.

Original languageEnglish (US)
Pages (from-to)997-1000
Number of pages4
JournalBiological psychiatry
Volume63
Issue number10
DOIs
StatePublished - May 15 2008

Keywords

  • Bipolar disorder
  • PICK1
  • d-serine
  • knockout mice
  • schizophrenia
  • serine racemase

ASJC Scopus subject areas

  • Biological Psychiatry

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