title: Behavioural alterations in male mice lacking the gene for D-aspartate oxidase.
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.
authors.affiliation: Department of Psychology, Institute for Behavioral Medicine Research, Ohio State University, Columbus, 43210, USA. Weil.20@osu.edu
authors.forename: Zachary M
authors.initials: ZM
authors.lastname: Weil
authors.forename: Alex S
authors.initials: AS
authors.lastname: Huang
authors.forename: Anne
authors.initials: A
authors.lastname: Beigneux
authors.forename: Paul M
authors.initials: PM
authors.lastname: Kim
authors.forename: Mark E
authors.initials: ME
authors.lastname: Molliver
authors.forename: Seth
authors.initials: S
authors.lastname: Blackshaw
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Young
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Nelson
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
mesh_terms: D000161:Acoustic Stimulation; D000311:Adrenal Glands / Q000201:enzymology; D000818:Animals; D001007:Anxiety / Q000201:enzymology*; D002531:Cerebellum / Q000201:enzymology; D050804:D-Aspartate Oxidase / Q000235:genetics / Q000378:metabolism*; D026603:D-Aspartic Acid / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology*; D046353:Immobility Response, Tonic / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009433:Neural Inhibition / Q000502:physiology; D010641:Phenotype; D013216:Reflex, Startle / Q000502:physiology*; D045442:Rotarod Performance Test; D013550:Swimming / Q000502:physiology
chemical_list: D026603:D-Aspartic Acid; D050804:D-Aspartate Oxidase