当前位置： SCI文献检索 > JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS期刊下所有文献 > D-Aspartate: An endogenous NMDA receptor agonist enriched in the developing brain with potential involvement in schizophrenia.

D-Aspartate: An endogenous NMDA receptor agonist enriched in the developing brain with potential involvement in schizophrenia.

Abstract：

:Free D-aspartate and D-serine occur at substantial levels in the mammalian brain. D-Serine is a physiological endogenous co-agonist for synaptic N-Methyl D-Aspartate (NMDA) receptors (NMDARs), and is involved in the pathophysiology of schizophrenia. Much less is known about the biological meaning of D-aspartate. D-Aspartate is present at high levels in the embryo brain and strongly decreases at post-natal phases. Temporal reduction of D-aspartate levels depends on the post-natal onset of D-aspartate oxidase (DDO), an enzyme able to selectively catabolize this D-amino acid. Pharmacological evidence indicates that D-aspartate binds to and activates NMDARs. Characterization of genetic and pharmacological mouse models with abnormally higher levels of D-aspartate has evidenced that increased D-aspartate enhances hippocampal NMDAR-dependent synaptic plasticity, dendritic morphology and spatial memory. In line with the hypothesis of a hypofunction of NMDARs in the pathogenesis of schizophrenia, it has been shown that increased D-aspartate levels also improve brain connectivity, produce corticostriatal adaptations resembling those observed after chronic haloperidol treatment, and protects against prepulse inhibition deficits and abnormal circuits activation induced by psychotomimetic drugs. In healthy humans, genetic variation predicting reduced expression of DDO in post-mortem prefrontal cortex is associated with greater prefrontal gray matter and activity during working memory. On the other side, evaluation of D-aspartate content in post-mortem patients with schizophrenia has shown a significant reduction of this D-amino acid in the prefrontal cortex and striatum. Generation of mouse models with reduced embryonic levels of D-aspartate may disclose unprecedented role for D-aspartate in developmental brain processes associated with vulnerability to psychotic-like symptoms.

journal_name

J Pharm Biomed Anal

journal_title

Journal of pharmaceutical and biomedical analysis

authors

Errico F,Mothet JP,Usiello A

doi

10.1016/j.jpba.2015.03.024

subject

Has Abstract

pub_date

2015-12-10 00:00:00

pages

7-17

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(15)00201-0

journal_volume

116

pub_type

杂志文章,评审

在线工具

D-Aspartate: An endogenous NMDA receptor agonist enriched in the developing brain with potential involvement in schizophrenia.