The GluN2B-Trp373 NMDA Receptor Variant is Associated with Autism-, Epilepsy-Related Phenotypes and Reduces NMDA Receptor Currents in Rats.
Neurochem Res
; 47(6): 1588-1597, 2022 Jun.
Article
en En
| MEDLINE
| ID: mdl-35181828
Autism spectrum disorder (ASD) is a neurodevelopmental condition with core clinical features of abnormal communication, social interactions, atypical intelligence, and a higher risk of epilepsy. Prior work has suggested that de novo heterozygous mutations in the GRIN2B gene that encodes the GluN2B subunit of N-methyl-D-aspartic acid receptors are likely linked to ASD. However, whether GLuN2B-Trp373 mutation derived from autistic individuals causes ASD-like behavioral aberrations in rats remains to be determined. Here, through in utero electroporation and in vivo studies, we conducted a battery of tests to examine ASD-associated behaviors, cognitive impairments, and susceptibility to pentylenetetrazol-induced seizures. Whole-cell patch recording was utilized to determine whether the GluN2B-Trp373 mutation influences GluN2B-containing NMDA receptor currents in rats. Results show that, behaviorally, GLuN2B-Trp373 mutant rats exhibited core behavioral manifestations of ASD, such as social interaction deficits, increases in stereotyped behaviors and anxiety stereotyped/repetitive, impaired spatial memory, and enhanced risk of pentylenetetrazol-induced seizures, consistent with many of the hallmarks of low-functioning ASD in humans. Functionally, the GluN2B-Trp373 mutation results in reduced GluN2B surface protein expression together with decreased hippocampal NMDA receptor currents. Collectively, our findings highlight that GluN2B-Trp373 mutations can drive the manifestation of ASD-associated symptoms via the suppression of NMDA receptor currents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Trastorno Autístico
/
Epilepsia
/
Trastorno del Espectro Autista
Tipo de estudio:
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
Neurochem Res
Año:
2022
Tipo del documento:
Article
País de afiliación:
China
Pais de publicación:
Estados Unidos