The MNK-SYNGAP1 axis in specific learning disorder: gene expression pattern and new perspectives

Specific learning disorder (SLD) is a neurodevelopmental disorder that significantly affects children's academic performance. This study aimed to investigate the expression levels of the MAP Kinase Interacting Serine/Threonine Kinase 1-2 (MNK1, MNK2), Synaptic Ras GTPase Activating Protein 1 (SYNGAP1) genes, and the long non-coding RNA Synaptic Ras GTPase Activating Protein 1-Anti Sense1 (SYNGAP1-AS1), which are believed to play a key role in neurodevelopmental pathways, in children with SLD. Understanding the role of these genes in synaptic plasticity and cognitive function may provide insights into the molecular mechanisms underlying SLD. This study included 38 children diagnosed with SLD and 35 healthy controls aged 6 to 16. RNA was isolated from blood samples, and gene expression levels were measured using quantitative polymerase chain reaction (qPCR). The statistical analysis was conducted to compare the expression levels between the SLD and control groups and within SLD subgroups based on severity and sex. MNK1 and SYNGAP1 expression levels were significantly upregulated in the SLD group compared to the control group (8.33-fold and 16.52-fold increase, respectively; p < 0.001). lncSYNGAP1-AS1 showed a 26.58-fold increase, while MNK2 was downregulated by 2.2-fold, although these changes were not statistically significant. No significant differences were observed between sexes or between the severity subgroups of SLD.

he upregulation of MNK1 and SYNGAP1 in children with SLD suggests their involvement in the neurodevelopmental pathways associated with cognitive processes such as learning and memory. These findings provide a foundation for future research into the molecular basis and potential therapeutic targets of SLD.

• SYNGAP1 is a key regulator of synaptic plasticity and learning, primarily functioning through Ras signaling inhibition. Its deficiency impairs long-term potentiation (LTP) and is associated with neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD) and intellectual disability. • The MAPK/ERK pathway plays a crucial role in learning and memory, and its dysregulation has been linked to several neurological conditions. MNK1/2 interacts with SYNGAP1 in synaptic signaling.

• This study is the first to demonstrate significant upregulation of SYNGAP1 and MKNK1 in children with SLD. • Understanding the role of the MKNK-SYNGAP1 axis may guide the development of targeted therapies aimed at enhancing synaptic plasticity to improve learning and memory outcomes in children with SLD.