| First Author | Bacq A | Year | 2020 |
| Journal | Mol Psychiatry | Volume | 25 |
| Issue | 9 | Pages | 2144-2161 |
| PubMed ID | 30089788 | Mgi Jnum | J:340892 |
| Mgi Id | MGI:6834653 | Doi | 10.1038/s41380-018-0132-3 |
| Citation | Bacq A, et al. (2020) Amygdala GluN2B-NMDAR dysfunction is critical in abnormal aggression of neurodevelopmental origin induced by St8sia2 deficiency. Mol Psychiatry 25(9):2144-2161 |
| abstractText | 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. |
