Impaired hippocampal NMDAR-LTP in a transgenic model of NSUN2-deficiency

Neurobiology of Disease

卷:163

Zafar I. Bashir¹  Shobbir Hussain²  Harry George² 

[1] Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, UK;

[2] School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol BS8 1TD, UK;

关键词: Autism;    ASC;    ASD;    Intellectual disability;    NSun2;    NMDAR-LTP;   

DOI  :  

来源: DOAJ

【 摘 要 】

Biallelic loss-of-function NSUN2 mutations have recently been associated with cases of Autism Spectrum Condition (ASC), and NSun2-deficiency was also previously shown to cause a severe autosomal recessive intellectually disability disorder syndrome in which patients can sometimes display autistic behaviour. It has been demonstrated that NSUN2 can control protein synthesis rates via direct regulation of RNA methylation, and it is therefore of interest that other studies have suggested protein synthesis-dependent synaptic plasticity dysregulation as a mechanism for learning difficulties in various other autism-expressing conditions and disorders. Here we investigated NMDAR-LTP in a murine transgenic model harbouring loss-of-function mutation in the NSun2 gene and find an impairment of a protein synthesis-dependent form of this synaptic plasticity pathway. Our findings support the idea that NMDAR-LTP mis-regulation may represent a previously underappreciated mechanism associated with autism phenotypes.

【 授权许可】

Unknown