Investigation of Alpha-Synuclein Expression During Developmental Stages of Cc2d1a Autistic Mice

Autism spectrum disorder (ASD) represents a complex neurodevelopmental condition characterized by a multifactorial etiology including both genetic, epigenetic and environmental factors.  Various brain regions, especially in the prefrontal, hippocampal and cerebellar cortex impacted by ASD. Multiple genes and genomic loci have association with autism including CC2D1A gene. The Cc2d1a knock-out mouse model has been shown to control several intracellular signaling pathways, including NF-κB activators, Protein Kinase B, neuronal differentiation and brain development as well as abnormalities in neural plasticity, spatial learning, decreased socialization, hyperactivity and anxiety. Alpha-synuclein gene (SNCA) is implicated in multiple disorders. Neurodevelopmental deficits are considered to be the primary mechanism underlying ASD and associated cognitive impairments and may be attributed to overexpression or inadequate expression of alpha-synuclein. Variations in alpha-synuclein expression in different cerebral regions may modulate neurogenesis and potentially contribute to the pathophysiology of ASD. In our previous study, SNCA expression profile was investigated in ASD families. Both SNCA gene expression and alpha-synuclein serum levels were decreased in ASD patients, similarly found to be significantly decreased in the mothers of the patients. We aimed to investigate alpha synuclein expressions from blood and hippocampus at 1 and 2 months old mice with Cc2d1a (+/-) and (+/+) genotypes. Our results showed that blood levels of alpha-synuclein is significantly decreased in the Cc2d1a (+/-) male mice. Although there is a decrease in hippocampus alpha-synuclein level in the Cc2d1a (+/-) male mice, it is not statistically significant. Interestingly, Cc2d1a (+/-) female mice showed increased alpha-synuclein level in both serum and hippocampus.  We may recommend that α-synuclein is differently regulated according to developmental stages in Cc2d1a male and female mice. 

Acknowledgement: This study was funded by Health Institutes of Türkiye (TUSEB, Grant Number: 31332).  

Key Words:  Autism Spectrum Disorders, Alpha Synuclein, Cc2d1a, Mice