http://www.cnr.it/ontology/cnr/individuo/prodotto/ID308975

D-Aspartate-Oxidase influences glutamatergic system homeostasis in mammalian brain (Articolo in rivista)

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D-Aspartate-Oxidase influences glutamatergic system homeostasis in mammalian brain (Articolo in rivista) (literal)

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Luigia Cristino, Livio Luongo, Marta Squillace, Giovanna Paolone, Dalila Mango, Sonia Piccinin, Elisa Zianni, Roberta Imperatore, Monica Iannotta, Francesco Longo, Francesco Errico, Angelo Luigi Vescovi, Michele Morari, Sabatino Maione, Fabrizio Gardoni, Robert Nisticò, Alessandro Usiello (2015)
D-Aspartate-Oxidase influences glutamatergic system homeostasis in mammalian brain
in Neurobiology of aging; Elsevier, New York (Stati Uniti d'America)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Luigia Cristino, Livio Luongo, Marta Squillace, Giovanna Paolone, Dalila Mango, Sonia Piccinin, Elisa Zianni, Roberta Imperatore, Monica Iannotta, Francesco Longo, Francesco Errico, Angelo Luigi Vescovi, Michele Morari, Sabatino Maione, Fabrizio Gardoni, Robert Nisticò, Alessandro Usiello (literal)

Rivista

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Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

We have investigated the relevance of D-Aspartate Oxidase (DDO), the only enzyme known to selectively degrade 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 NMDA receptor (NMDAR) stimulation, we documented in Ddo knockouts severe age-dependent structural and functional alterations mirrored by expression of active caspase 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 AMPA/NMDA ratio. These effects, all of which converged on a progressive hypo-responsiveness at NMDAR sites, functionally resulted in a greater vulnerability to phencyclidine-induced prepulse inhibition deficits in mutants. In conclusion, our results indicate that DDO, by strictly regulating D-Asp levels, impacts on the homeostasis of glutamatergic system thus preventing accelerated neurodegenerative processes. (literal)

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