PT  - JOURNAL ARTICLE
AU  - Francesco Errico
AU  - Silvia Rossi
AU  - Francesco Napolitano
AU  - Valeria Catuogno
AU  - Enza Topo
AU  - Gilberto Fisone
AU  - Antimo D&#039;Aniello
AU  - Diego Centonze
AU  - Alessandro Usiello
TI  - &lt;span class=&quot;sc&quot;&gt;d&lt;/span&gt;-Aspartate Prevents Corticostriatal Long-Term Depression and Attenuates Schizophrenia-Like Symptoms Induced by Amphetamine and MK-801
AID  - 10.1523/JNEUROSCI.1618-08.2008
DP  - 2008 Oct 08
TA  - The Journal of Neuroscience
PG  - 10404--10414
VI  - 28
IP  - 41
4099  - http://www.jneurosci.org/content/28/41/10404.short
4100  - http://www.jneurosci.org/content/28/41/10404.full
SO  - J. Neurosci.2008 Oct 08; 28
AB  - 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.