D-aspartate regulates melanocortin formation and function: Behavioral alterations in D-aspartate oxidase-deficient mice

被引：55

作者：

Huang, AS

Beigneux, A

Weil, ZM

Kim, PM

Molliver, ME

Blackshaw, S

Nelson, RJ

Young, SG

Snyder, SH

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[4] Univ Calif Los Angeles, David Geffen Sch Med, Div Cardiol, Dept Med, Los Angeles, CA 90095 USA

[5] Ohio State Univ, Dept Psychol, Inst Behav Med Res, Columbus, OH 43210 USA

[6] Ohio State Univ, Dept Neurosci, Inst Behav Med Res, Columbus, OH 43210 USA

来源：

JOURNAL OF NEUROSCIENCE | 2006年 / 26卷 / 10期

关键词：

amino acid; neuroendocrine; knock-out mice; aspartate; turnover; behavior; proopiomelanocortin (POMC);

D O I：

10.1523/JNEUROSCI.5060-05.2006

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

D-Aspartate, an abundant D-amino acid enriched in neuroendocrine tissues, can be degraded by D-aspartate oxidase (Ddo). To elucidate the function of D-aspartate, we generated mice with targeted deletion of Ddo (Ddo(-/-)) and observe massive but selective augmentations of D-aspartate in various tissues. The pituitary intermediate lobe, normally devoid of D-aspartate from endogenous Ddo expression, manifests pronounced increases of immunoreactive D-aspartate in Ddo(-/-) mice. Ddo(-/-) mice show markedly diminished synthesis and levels of pituitary proopiomelanocortin/alpha-MSH, associated with decreased melanocortin-dependent behaviors. Therefore, Ddo is the endogenous enzyme that degrades D-aspartate, and Ddo-enriched organs, low in D-aspartate, may represent areas of high turnover where D-aspartate may be physiologically important.

引用

页码：2814 / 2819

页数：6

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