Dysfunctional d-aspartate metabolism in BTBR mouse model of idiopathic autism.
Autism spectrum disorder
NMDA receptors
d-aspartate
d-aspartate oxidase
d-serine
Journal
Biochimica et biophysica acta. Proteins and proteomics
ISSN: 1878-1454
Titre abrégé: Biochim Biophys Acta Proteins Proteom
Pays: Netherlands
ID NLM: 101731734
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
16
05
2020
revised:
22
07
2020
accepted:
31
07
2020
pubmed:
28
8
2020
medline:
15
12
2020
entrez:
28
8
2020
Statut:
ppublish
Résumé
Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental conditions characterized by impairment in social interaction, deviance in communication, and repetitive behaviors. Dysfunctional ionotropic NMDA and AMPA receptors, and metabotropic glutamate receptor 5 activity at excitatory synapses has been recently linked to multiple forms of ASD. Despite emerging evidence showing that d-aspartate and d-serine are important neuromodulators of glutamatergic transmission, no systematic investigation on the occurrence of these D-amino acids in preclinical ASD models has been carried out. Through HPLC and qPCR analyses we investigated d-aspartate and d-serine metabolism in the brain and serum of four ASD mouse models. These include BTBR mice, an idiopathic model of ASD, and Cntnap2 Biochemical and gene expression mapping in Cntnap2 Our results demonstrated the presence of disrupted d-aspartate metabolism in a widely used animal model of idiopathic ASD. Overall, this work calls for a deeper investigation of D-amino acids in the etiopathology of ASD and related developmental disorders.
Sections du résumé
BACKGROUND
Autism spectrum disorders (ASD) comprise a heterogeneous group of neurodevelopmental conditions characterized by impairment in social interaction, deviance in communication, and repetitive behaviors. Dysfunctional ionotropic NMDA and AMPA receptors, and metabotropic glutamate receptor 5 activity at excitatory synapses has been recently linked to multiple forms of ASD. Despite emerging evidence showing that d-aspartate and d-serine are important neuromodulators of glutamatergic transmission, no systematic investigation on the occurrence of these D-amino acids in preclinical ASD models has been carried out.
METHODS
Through HPLC and qPCR analyses we investigated d-aspartate and d-serine metabolism in the brain and serum of four ASD mouse models. These include BTBR mice, an idiopathic model of ASD, and Cntnap2
RESULTS
Biochemical and gene expression mapping in Cntnap2
CONCLUSIONS
Our results demonstrated the presence of disrupted d-aspartate metabolism in a widely used animal model of idiopathic ASD.
GENERAL SIGNIFICANCE
Overall, this work calls for a deeper investigation of D-amino acids in the etiopathology of ASD and related developmental disorders.
Identifiants
pubmed: 32853769
pii: S1570-9639(20)30178-3
doi: 10.1016/j.bbapap.2020.140531
pii:
doi:
Substances chimiques
Biomarkers
0
D-Aspartic Acid
4SR0Q8YD1X
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
140531Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest None.