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

Biallelic loss-of-function NSUN2 mutations have recently been associated with cases of Autism Spectrum Con-dition (ASC), and NSun2-deficiency was also previously shown to cause a severe autosomal recessive intellec-tually 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 dysregu-lation 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.

Automated summary

Biallelic loss-of-function NSUN2 mutations have been associated with Autism Spectrum Condition (ASC), and NSun2-deficiency can cause intellectually disability disorder syndrome, which can sometimes display autistic behavior. The study suggests that protein synthesis-dependent synaptic plasticity dysregulation may be a mechanism associated with autism phenotypes.