Since their discovery in the mammalian CNS, D-aspartate and D-serine have aroused a strong interest with regard to their role as putative neuromodulatory molecules. Whereas the functional role of D-serine as an endogenous coagonist of NMDA receptors (NMDARs) has been elucidated, the biological significance of D-aspartate in the brain is still mostly unclear. In the present study, we demonstrated that nonphysiological high levels of D-aspartate (1) increased in vivo NMDAR activity, (2) attenuated prepulse inhibition deficits induced by amphetamine and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate], (3) produced striatal adaptations of glutamate synapses resembling those observed after chronic haloperidol treatment, and (4) enhanced hippocampal NMDAR-dependent memory. This evidence was obtained using two different experimental strategies that produced an abnormal increase of endogenous D-aspartate levels in the mouse: a genetic approach based on the targeted deletion of the D-aspartate oxidase gene and a pharmacological approach based on oral administration of D-aspartate. This work provides in vivo evidence of a neuromodulatory role exerted by D-aspartate on NMDAR signaling and raises the intriguing hypothesis that also this D-amino acid, like D-serine, could be used as a therapeutic agent in the treatment of schizophrenia-related symptoms.

Errico, F., Rossi, S., Napolitano, F., Catuogno, V., Topo, E., Fisone, G., et al. (2008). D-aspartate prevents corticostriatal long-term depression and attenuates schizophrenia-like symptoms induced by amphetamine and MK-801. THE JOURNAL OF NEUROSCIENCE, 28(41), 10404-10414 [10.1523/JNEUROSCI.1618-08.2008].

D-aspartate prevents corticostriatal long-term depression and attenuates schizophrenia-like symptoms induced by amphetamine and MK-801

CENTONZE, DIEGO;
2008-10-08

Abstract

Since their discovery in the mammalian CNS, D-aspartate and D-serine have aroused a strong interest with regard to their role as putative neuromodulatory molecules. Whereas the functional role of D-serine as an endogenous coagonist of NMDA receptors (NMDARs) has been elucidated, the biological significance of D-aspartate in the brain is still mostly unclear. In the present study, we demonstrated that nonphysiological high levels of D-aspartate (1) increased in vivo NMDAR activity, (2) attenuated prepulse inhibition deficits induced by amphetamine and MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohepten-5,10-imine hydrogen maleate], (3) produced striatal adaptations of glutamate synapses resembling those observed after chronic haloperidol treatment, and (4) enhanced hippocampal NMDAR-dependent memory. This evidence was obtained using two different experimental strategies that produced an abnormal increase of endogenous D-aspartate levels in the mouse: a genetic approach based on the targeted deletion of the D-aspartate oxidase gene and a pharmacological approach based on oral administration of D-aspartate. This work provides in vivo evidence of a neuromodulatory role exerted by D-aspartate on NMDAR signaling and raises the intriguing hypothesis that also this D-amino acid, like D-serine, could be used as a therapeutic agent in the treatment of schizophrenia-related symptoms.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/26 - Neurologia
English
Con Impact Factor ISI
Schizophrenia; Acoustic Stimulation; Hippocampus; Corpus Striatum; Central Nervous System Stimulants; Dizocilpine Maleate; Startle Reaction; Mice, Knockout; Animals; Receptors, N-Methyl-D-Aspartate; Cerebral Cortex; D-Aspartate Oxidase; D-Aspartic Acid; Amphetamine; Neuronal Plasticity; Excitatory Amino Acid Antagonists; Mice; Tissue Distribution; Mice, Inbred C57BL; Memory; Brain; Long-Term Synaptic Depression; Drug Administration Schedule; Synaptic Transmission
Errico, F., Rossi, S., Napolitano, F., Catuogno, V., Topo, E., Fisone, G., et al. (2008). D-aspartate prevents corticostriatal long-term depression and attenuates schizophrenia-like symptoms induced by amphetamine and MK-801. THE JOURNAL OF NEUROSCIENCE, 28(41), 10404-10414 [10.1523/JNEUROSCI.1618-08.2008].
Errico, F; Rossi, S; Napolitano, F; Catuogno, V; Topo, E; Fisone, G; D'Aniello, A; Centonze, D; Usiello, A
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/41485
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