Behavioural alterations in male mice lacking the gene for d-aspartate oxidase

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

Research output: Contribution to journalArticle

Abstract

d-serine and d-aspartate are important regulators of mammalian physiology. d-aspartate is found in nervous and endocrine tissue, specifically in hypothalamic supraoptic and paraventricular nuclei, pituitary, and adrenal medullary cells. Endogenous d-aspartate is selectively degraded by d-aspartate oxidase. We previously reported that adult male mice lacking the gene for d-aspartate oxidase (Ddo-/- mice) display elevated concentrations of d-aspartate in several neuronal and neuroendocrine tissues as well as impaired sexual performance and altered autogrooming behaviour. In the present study, we analyzed behaviours relevant to affect, cognition, and motor control in Ddo-/- mice. Ddo-/- mice display deficits in sensorimotor gating and motor coordination as well as reduced immobility in the forced swim test. Basal corticosterone concentrations are elevated. The Ddo-/- mice have d-aspartate immunoreactive cells in the cerebellum and adrenal glands that are not observed in the wild-type mice. However, no differences in anxiety-like behaviour are detected in open field or light-dark preference tests. Also, Ddo-/- mice do not differ from wild-type mice in either passive avoidance or spontaneous alternation tasks. Although many of these behavioural deficits may be due to the lack of Ddo during development, our results are consistent with the widespread distribution of d-aspartate and the hypothesis that endogenous d-aspartate serves diverse behavioural functions.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalBehavioural Brain Research
Volume171
Issue number2
DOIs
StatePublished - Aug 10 2006

Fingerprint

Aspartic Acid
Oxidoreductases
Genes
Sensory Gating
Nerve Tissue
Supraoptic Nucleus
Adrenal Glands
Corticosterone
Cerebellum
Serine
Cognition
Anxiety
Light

Keywords

  • Behavioural phenotyping
  • d-amino acids
  • d-aspartate
  • d-aspartate oxidase
  • Knockout mice
  • Prepulse inhibition
  • RotoRod

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Behavioural alterations in male mice lacking the gene for d-aspartate oxidase. / Weil, Zachary M.; Huang, Alex S.; Beigneux, Anne; Kim, Paul; Molliver, Mark E.; Blackshaw, Seth; Young, Stephen G.; Nelson, Randy J.; Snyder, Solomon H.

In: Behavioural Brain Research, Vol. 171, No. 2, 10.08.2006, p. 295-302.

Research output: Contribution to journalArticle

Weil, Zachary M. ; Huang, Alex S. ; Beigneux, Anne ; Kim, Paul ; Molliver, Mark E. ; Blackshaw, Seth ; Young, Stephen G. ; Nelson, Randy J. ; Snyder, Solomon H. / Behavioural alterations in male mice lacking the gene for d-aspartate oxidase. In: Behavioural Brain Research. 2006 ; Vol. 171, No. 2. pp. 295-302.
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