Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase

Yurika Miyoshi, Ryuichi Konno, Jumpei Sasabe, Kyoko Ueno, Yosuke Tojo, Masashi Mita, Sadakazu Aiso, Kenji Hamase

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

For elucidation of the regulation mechanisms of intrinsic amounts of D-serine (D-Ser) which modulates the neuro-transmission of N-methyl-D-aspartate receptors in the brain, mutant animals lacking serine racemase (SRR) and D-amino acid oxidase (DAO) were established, and the amounts of D-Ser in the tissues and physiological fluids were determined. D-Ser amounts in the frontal brain areas were drastically decreased followed by reduced SRR activity. On the other hand, a moderate but significant decrease in D-Ser amounts was observed in the cerebellum and spinal cord of SRR knock-out (SRR-/-) mice compared with those of control mice, although the amounts of D-Ser in these tissues were low. The amounts of D-Ser in the brain and serum were not altered with aging. To clarify the uptake of exogenous D-Ser into the brain tissues, we have determined the D-Ser of SRR-/- mice after oral administration of D-Ser for the first time, and a drastic increase in D-Ser amounts in all the tested tissues was observed. Because both DAO and SRR are present in some brain areas, we have established the double mutant mice lacking SRR and DAO for the first time, and the contribution of both enzymes to the intrinsic D-Ser amounts was investigated. In the frontal brain, most of the intrinsic D-Ser was biosynthesized by SRR. On the other hand, half of the D-Ser present in the hindbrain was derived from the biosynthesis by SRR. These results indicate that the regulation of intrinsic D-Ser amounts is different depending on the tissues and provide useful information for the development of treatments for neuronal diseases.

Original languageEnglish
Pages (from-to)1919-1931
Number of pages13
JournalAmino Acids
Volume43
Issue number5
DOIs
Publication statusPublished - 2012 Nov 1
Externally publishedYes

Fingerprint

D-Amino-Acid Oxidase
Serine
Brain
Tissue
serine racemase
Biosynthesis
N-Methyl-D-Aspartate Receptors
Animals
Aging of materials

Keywords

  • 2D-HPLC
  • D-Amino acid oxidase
  • D-Serine
  • Serine racemase

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Miyoshi, Y., Konno, R., Sasabe, J., Ueno, K., Tojo, Y., Mita, M., ... Hamase, K. (2012). Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase. Amino Acids, 43(5), 1919-1931. https://doi.org/10.1007/s00726-012-1398-4

Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase. / Miyoshi, Yurika; Konno, Ryuichi; Sasabe, Jumpei; Ueno, Kyoko; Tojo, Yosuke; Mita, Masashi; Aiso, Sadakazu; Hamase, Kenji.

In: Amino Acids, Vol. 43, No. 5, 01.11.2012, p. 1919-1931.

Research output: Contribution to journalArticle

Miyoshi, Y, Konno, R, Sasabe, J, Ueno, K, Tojo, Y, Mita, M, Aiso, S & Hamase, K 2012, 'Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase', Amino Acids, vol. 43, no. 5, pp. 1919-1931. https://doi.org/10.1007/s00726-012-1398-4
Miyoshi, Yurika ; Konno, Ryuichi ; Sasabe, Jumpei ; Ueno, Kyoko ; Tojo, Yosuke ; Mita, Masashi ; Aiso, Sadakazu ; Hamase, Kenji. / Alteration of intrinsic amounts of D-serine in the mice lacking serine racemase and D-amino acid oxidase. In: Amino Acids. 2012 ; Vol. 43, No. 5. pp. 1919-1931.
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