Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency.
Mol Psychiatry
; 25(9): 2144-2161, 2020 09.
Article
in En
| MEDLINE
| ID: mdl-30089788
ABSTRACT
Aggression is frequently observed in neurodevelopmental psychiatric disorders such as schizophrenia, autism, and bipolar disorder. Due to a lack of understanding of its underlying mechanisms, effective treatments for abnormal aggression are still missing. Recently, genetic variations in Sialyltransferase 2 (St8sia2) have been linked to these disorders and aggression. Here we identify abnormal aggressive behaviors and concomitant blunted fear learning in St8sia2 knockout (-/-) mice. It is worth noting that the amygdala of St8sia2-/- mice shows diminished threat-induced activation, as well as alterations in synaptic structure and function, including impaired GluN2B-containing NMDA receptor-mediated synaptic transmission and plasticity. Pharmacological rescue of NMDA receptor activity in the amygdala of St8sia2-/- mice with the partial agonist D-cycloserine restores synaptic plasticity and normalizes behavioral aberrations. Pathological aggression and associated traits were recapitulated by specific amygdala neonatal St8sia2 silencing. Our results establish a developmental link between St8sia2 deficiency and a pathological aggression syndrome, specify synaptic targets for therapeutic developments, and highlight D-cycloserine as a plausible treatment.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sialyltransferases
/
Receptors, N-Methyl-D-Aspartate
/
Aggression
/
Amygdala
Limits:
Animals
Language:
En
Journal:
Mol Psychiatry
Journal subject:
BIOLOGIA MOLECULAR
/
PSIQUIATRIA
Year:
2020
Document type:
Article
Affiliation country:
Suiza