Alleviation of N-Methyl-D-Aspartate Receptor-Dependent Long-Term Depression via Regulation of the Glycogen Synthase Kinase-3ß Pathway in the Amygdala of a Valproic Acid-Induced Animal Model of Autism.
Mol Neurobiol
; 54(7): 5264-5276, 2017 09.
Article
in En
| MEDLINE
| ID: mdl-27578017
ABSTRACT
The amygdala plays crucial roles in socio-emotional behavior and cognition, both of which are abnormal in autism spectrum disorder (ASD). Valproic acid (VPA)-exposed rat offspring have demonstrated ASD phenotypes and amygdala excitatory/inhibitory imbalance. However, the role of glutamatergic synapses in this imbalance remains unclear. In this study, we used a VPA-induced ASD-like model to assess glutamatergic synapse-dependent long-term depression (LTD) and depotentiation (DPT) in the amygdala. We first confirmed that the VPA-exposed offspring exhibited sociability deficits, anxiety, depression-like behavior, and abnormal nociception thresholds. Then, electrophysiological examination showed a significantly decreased paired-pulse ratio in the amygdala. In addition, both NMDA-dependent LTD and DPT were absent from the amygdala. Furthermore, we found that the levels of glycogen synthase kinase3ß (GSK-3ß) phosphorylation and ß-catenin were significantly higher in the amygdala of the experimental animals than in the controls. Local infusion of phosphatidylinositol 3-kinase (PI3K) inhibitor wortmannin into the amygdala reversed the increased phosphorylation level and impaired social behavior. Taken together, the results suggested that NMDA receptor-related synaptic plasticity is dysfunctional in VPA-exposed offspring. In addition, GSK-3ß in the amygdala is critical for synaptic plasticity at the glutamatergic synapses and is related to social behavior. Its role in the underlying mechanism of ASD merits further investigation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Autistic Disorder
/
Valproic Acid
/
Receptors, N-Methyl-D-Aspartate
/
Enzyme Inhibitors
/
Neuronal Plasticity
Limits:
Animals
Language:
En
Journal:
Mol Neurobiol
Journal subject:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Taiwan