D-Amino Acids pp 219-237 | Cite as

Neuromodulatory Activity of d-Aspartate in Mammals

  • Francesco ErricoEmail author
  • Alessandro Usiello


d-aspartate is transiently present in the mammalian brain since it substantially occurs in embryonic phases and strongly decreases after birth, due to the postnatal activity of the catabolizing enzyme d-aspartate oxidase (DDO). Pharmacological evidence indicates that d-aspartate binds to and activates NMDA receptors (NMDARs). To decipher the function of d-aspartate in mammals, genetic and pharmacological mouse models with nonphysiological high levels of this d-amino acid have been generated. Their characterization has evidenced that increased d-aspartate enhances hippocampal NMDAR-dependent synaptic plasticity, dendritic morphology, and spatial memory. In line with the hypothesis of a NMDAR hypofunction in the pathogenesis of schizophrenia, it has been also shown that increased d-aspartate produces corticostriatal adaptations resembling those observed after chronic haloperidol treatment, and protects against prepulse inhibition deficits induced by psychotomimetic drugs. Moreover, a study in healthy humans has demonstrated that genetic variation in DDO gene, predicting potential increase in d-aspartate levels in postmortem prefrontal cortex, is associated with greater prefrontal gray matter and activity during working memory. Interestingly, a significant reduction of d-aspartate content has been detected in the postmortem brain of patients with schizophrenia. In line with a dichotomous effect of NMDAR stimulation on brain physiology, constitutive elevation of d-aspartate levels is also associated with detrimental effects, including precocious hippocampal age-related deterioration. Based on the agonistic role of d-aspartate on NMDARs and on its abundance during prenatal life, future studies will be crucial to address the effect of this molecule on developmental processes controlled by NMDARs.


d-aspartate d-aspartate oxidase NMDA receptor Mouse models 


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Copyright information

© Springer Japan 2016

Authors and Affiliations

  1. 1.Laboratory of Behavioural NeuroscienceCeinge Biotecnologie AvanzateNaplesItaly
  2. 2.Department of Molecular Medicine and Medical BiotechnologyUniversity of Naples “Federico II”NaplesItaly
  3. 3.Department of Environmental, Biological and Pharmaceutical Sciences and TechnologiesThe Second University of Naples (SUN)CasertaItaly

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