Developmental and sex-specific expression of alpha-synuclein in blood and hippocampus of Cc2d1a mice: Implications for autism spectrum disorders.

PURPOSE: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by deficits in social interaction and the presence of restricted, repetitive behaviors. It involves alterations in brain structure and function due to a combination of genetic, epigenetic, and environmental factors. The Cc2d1a gene is a recently identified candidate gene implicated in ASD. Alpha-synuclein (Snca), a presynaptic neuronal protein classically linked to neurodegeneration, has recently been proposed as a potential player in neurodevelopmental disorders. This study investigated the expression of the Snca gene and protein in a Cc2d1a mouse model of autism, focusing on sex-based and developmental stage differences.

METHODS

Blood and hippocampal tissues were collected from male and female mice with heterozygous (+/-) and wild-type (+/+) genotypes at postnatal days 14, 30, and 60. Gene and protein expression levels of Snca were analyzed using quantitative real-time PCR (qRT-PCR) and ELISA. Behavioral tests were used to assess locomotor activity and anxiety.

RESULTS

Male mice displayed higher locomotor activity than females in the open field test across developmental stages. At postnatal day 60, Snca mRNA expression increased in heterozygous females but decreased in wild-type females, whereas the opposite pattern was observed in males. Similar genotype- and sex-dependent trends were detected in hippocampal tissue. At the protein level, α-synuclein expression was consistently lower in the female hippocampus compared to males, while blood α-synuclein levels did not differ significantly between sexes.

CONCLUSION

These findings demonstrate developmental and sex-specific differences in Snca expression in an ASD mouse model. Alpha-synuclein may serve as a promising biomarker for further studies in ASD pathophysiology.