d-Aspartate oxidase influences glutamatergic system homeostasis in mammalian brain

Neurobiology of Aging
Luigia CristinoAlessandro Usiello

Abstract

We have investigated the relevance of d-aspartate oxidase, the only enzyme known to selectively degrade d-aspartate (d-Asp), in modulating glutamatergic system homeostasis. Interestingly, the lack of the Ddo gene, by raising d-Asp content, induces a substantial increase in extracellular glutamate (Glu) levels in Ddo-mutant brains. Consistent with an exaggerated and persistent N-methyl-d-aspartate receptor (NMDAR) stimulation, we documented in Ddo knockouts severe age-dependent structural and functional alterations mirrored by expression of active caspases 3 and 7 along with appearance of dystrophic microglia and reactive astrocytes. In addition, prolonged elevation of d-Asp triggered in mutants alterations of NMDAR-dependent synaptic plasticity associated to reduction of hippocampal GluN1 and GluN2B subunits selectively located at synaptic sites and to increase in the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-to-N-methyl-d-aspartate ratio. These effects, all of which converged on a progressive hyporesponsiveness at NMDAR sites, functionally resulted in a greater vulnerability to phencyclidine-induced prepulse inhibition deficits in mutants. In conclusion, our results indicate that d-aspartate oxidase, by strictly reg...Continue Reading

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Citations

Apr 15, 2015·Journal of Pharmaceutical and Biomedical Analysis·Francesco ErricoAlessandro Usiello
May 17, 2015·Progress in Neuro-psychopharmacology & Biological Psychiatry·Andrea de BartolomeisFelice Iasevoli
Feb 12, 2020·Applied Microbiology and Biotechnology·Shouji Takahashi
Jan 10, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Gianluca MollaLoredano Pollegioni
Dec 29, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Stephen D SkaperPietro Giusti
Sep 9, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Tommaso NuzzoAlessandro Usiello
Aug 28, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Tommaso NuzzoAlessandro Usiello
Feb 9, 2021·Journal of Alzheimer's Disease : JAD·Luciano PiubelliLoredano Pollegioni
Mar 13, 2021·The Biochemical Journal·Herman Wolosker, Inna Radzishevsky
Jun 20, 2020·Biochimica Et Biophysica Acta. Proteins and Proteomics·Vincenzo PuggioniSilvia Sacchi
Mar 3, 2021·The FEBS Journal·Valentina RabattoniSilvia Sacchi
Apr 4, 2021·International Journal of Molecular Sciences·Nicola AlessioFrancesca Guida
Jun 22, 2021·Toxicology Reports·Azeez Olakunle IsholaMoyosore Salihu Ajao
Jul 13, 2021·Frontiers in Molecular Biosciences·Loredano PollegioniGiulia Murtas

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