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Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals

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Τίτλος: Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals
Συγγραφείς: Errico, F, NISTICO', ROBERT GIOVANNI, Di Giorgio, A, Squillace, M, Vitucci, D, Galbusera, A, Piccinin, S, Mango, D, Fazio, L, Middei, S, Trizio, S, MERCURI, NICOLA BIAGIO, Teule, M, CENTONZE, DIEGO, Gozzi, A, Blasi, G, Bertolino, A, Usiello, A.
Συνεισφορές: Errico, F, Nistico', Rg, Di Giorgio, A, Squillace, M, Vitucci, D, Galbusera, A, Piccinin, S, Mango, D, Fazio, L, Middei, S, Trizio, S, Mercuri, Nb, Teule, M, Centonze, D, Gozzi, A, Blasi, G, Bertolino, A, Usiello, A
Στοιχεία εκδότη: Nature Pub. Group
US
Έτος έκδοσης: 2014
Συλλογή: Universitá degli Studi di Roma "Tor Vergata": ART - Archivio Istituzionale della Ricerca
Θεματικοί όροι: Settore BIO/14 - FARMACOLOGIA
Περιγραφή: D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
Relation: info:eu-repo/semantics/altIdentifier/pmid/25072322; info:eu-repo/semantics/altIdentifier/wos/WOS:000344826700014; volume:4; firstpage:e417; lastpage:e417; journal:TRANSLATIONAL PSYCHIATRY; https://hdl.handle.net/2108/87747
DOI: 10.1038/tp.2014.59
Διαθεσιμότητα: https://hdl.handle.net/2108/87747
https://doi.org/10.1038/tp.2014.59
Rights: info:eu-repo/semantics/openAccess ; license:Copyright dell'editore
Αριθμός Καταχώρησης: edsbas.DB149ED0
Βάση Δεδομένων: BASE
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  Data: Free D-aspartate regulates neuronal dendritic morphology, synaptic plasticity, gray matter volume and brain activity in mammals
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  Data: Errico, F<br />Nistico', Rg<br />Di Giorgio, A<br />Squillace, M<br />Vitucci, D<br />Galbusera, A<br />Piccinin, S<br />Mango, D<br />Fazio, L<br />Middei, S<br />Trizio, S<br />Mercuri, Nb<br />Teule, M<br />Centonze, D<br />Gozzi, A<br />Blasi, G<br />Bertolino, A<br />Usiello, A
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  Data: D-aspartate (D-Asp) is an atypical amino acid, which is especially abundant in the developing mammalian brain, and can bind to and activate N-methyl-D-Aspartate receptors (NMDARs). In line with its pharmacological features, we find that mice chronically treated with D-Asp show enhanced NMDAR-mediated miniature excitatory postsynaptic currents and basal cerebral blood volume in fronto-hippocampal areas. In addition, we show that both chronic administration of D-Asp and deletion of the gene coding for the catabolic enzyme D-aspartate oxidase (DDO) trigger plastic modifications of neuronal cytoarchitecture in the prefrontal cortex and CA1 subfield of the hippocampus and promote a cytochalasin D-sensitive form of synaptic plasticity in adult mouse brains. To translate these findings in humans and consistent with the experiments using Ddo gene targeting in animals, we performed a hierarchical stepwise translational genetic approach. Specifically, we investigated the association of variation in the gene coding for DDO with complex human prefrontal phenotypes. We demonstrate that genetic variation predicting reduced expression of DDO in postmortem human prefrontal cortex is mapped on greater prefrontal gray matter and activity during working memory as measured with MRI. In conclusion our results identify novel NMDAR-dependent effects of D-Asp on plasticity and physiology in rodents, which also map to prefrontal phenotypes in humans.
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