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

Alex S. Huang; Anne Beigneux; Zachary M. Weil; Paul M. Kim; Mark E. Molliver; Seth Blackshaw; Randy J. Nelson; Stephen G. Young; Solomon H. Snyder

doi:10.1523/JNEUROSCI.5060-05.2006

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

Alex S. Huang, Anne Beigneux, Zachary M. Weil, Paul M. Kim, Mark E. Molliver, Seth Blackshaw, Randy J. Nelson, Stephen G. Young, Solomon H. Snyder

School of Medicine

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

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/α-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.

Original language	English (US)
Pages (from-to)	2814-2819
Number of pages	6
Journal	Journal of Neuroscience
Volume	26
Issue number	10
DOIs	https://doi.org/10.1523/JNEUROSCI.5060-05.2006
State	Published - Mar 8 2006

Keywords

Amino acid
Aspartate
Behavior
Knock-out mice
Neuroendocrine
Proopiomelanocortin (POMC)
Turnover

ASJC Scopus subject areas

General Neuroscience

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10.1523/JNEUROSCI.5060-05.2006

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title = "D-Aspartate regulates melanocortin formation and function: Behavioral alterations in D-aspartate oxidase-deficient mice",

abstract = "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/α-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.",

keywords = "Amino acid, Aspartate, Behavior, Knock-out mice, Neuroendocrine, Proopiomelanocortin (POMC), Turnover",

author = "Huang, {Alex S.} and Anne Beigneux and Weil, {Zachary M.} and Kim, {Paul M.} and Molliver, {Mark E.} and Seth Blackshaw and Nelson, {Randy J.} and Young, {Stephen G.} and Snyder, {Solomon H.}",

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AU - Huang, Alex S.

AU - Beigneux, Anne

AU - Weil, Zachary M.

AU - Kim, Paul M.

AU - Molliver, Mark E.

AU - Blackshaw, Seth

AU - Nelson, Randy J.

AU - Young, Stephen G.

AU - Snyder, Solomon H.

PY - 2006/3/8

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N2 - 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/α-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.

AB - 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/α-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.

KW - Amino acid

KW - Aspartate

KW - Behavior

KW - Knock-out mice

KW - Neuroendocrine

KW - Proopiomelanocortin (POMC)

KW - Turnover

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

Abstract

Keywords

ASJC Scopus subject areas

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