Examination of the levels of serine protease and related molecules in children with autism spectrum disorder

Objective: In this study, the role of serine proteases and related molecules in the etiopathogenesis of Autism Spectrum Disorder (ASD) and the investigation of the relationship between the severity of autism symptoms and behavioral problems have been aimed. A number of serine proteases and serpins have been shown to affect synaptic plasticity. Synaptic plasticity is the ability of neurons to modify the strength of their connections in response to activity, and it is necessary for learning, memory, and the establishment and execution of cognitive functions. It has been shown that autism is accompanied by impairments in learning, memory and higher cognitive functions. Motopsin, agrin, C-terminal agrin fragment (CAF), tissue plasminogen activator (tPA), neuroserpin and plasminogen activator inhibitor 1 (PAI-1) are molecules associated with serine proteases. These molecules have a regulatory role in modulating emotions, behavior and cognitive activities through synaptic plasticity. In this study, these molecules were selected and their serum levels were measured. Based on this, in the present study, motopsin, agrin, C-terminal agrin fragment (CAF), tissue plasminogen activator (tPA), neuroserpin, and plasminogen activator inhibitor 1 (PAI-1) have been selected as serine proteases and associated molecules that modulate emotion and behaviour through synaptic plasticity and have a regulatory role in cognitive activities. Serum levels of selected molecules were measured in the study. Materials and Methods: This study is cross-sectional. In accordance with the inclusion and exclusion criteria, 44 children with ASD between the ages of 2 and 6 were selected to form the experimental group and 43 healthy children matched with the ASD group in terms of age and gender to form the control group. The severity of symptoms and behavioral problems in children diagnosed with ASD has been assessed using the Childhood Autism Rating Scale (CARS), Autism Behavior Evaluation Checklist (ABC), and the Repetitive Behavior Scale- Revised Form-Turkish Version (RBS-R-TV). Venous blood samples were taken from children in both groups and serum motopsin, agrin, CAF, tPA, neuroserpine and PAI-1 levels were measured by ELISA method. Results: Serum motopsin, agrin, CAF, tPA, neuroserpine and PAI-1 levels were found to be significantly lower in the ASD group compared to the control group. There was no significant difference between the severity of ASD and serum motopsin, agrin, CAF, tPA, neuroserpine and PAI-1 levels. While a positive, moderate, and significant relationship was found between CARS imitation subscale and motopsin, negative, moderately strong, significant relationships were found between CARS-listening response, taste-smelling-touch response and use, activity level subscales and pain. A similar, moderately strong and significant relationship was found between ABC sensory subscale scores and motopsin. An inverse, moderately strong, significant correlation was found between the RBC-R-TV selfharm subscale. Conclusion: Our findings showed that serine protease and related molecules involved in synaptic plasticity may play a role in the etiopathogenesis of ASD. Since ASD is a disorder characterized by deterioration in various parts of the brain, the relationship between subscale scores evaluating different parts of the brain and blood parameters was also found to be quite complex. Further studies, including neurophysiological, neurobiological, neuroimaging and serum studies, are needed to better evaluate the role of blood parameters evaluated in the study in the etiopathogenesis of ASD and to better understand their relationship with total scale scores and subscale scores indicating ASD symptom severity. The use of potential biochemical markers that point to specific mechanisms of impaired neurodevelopment helps define subtypes of autism to treat it. Thus, it will help tailor treatment or prevention strategies for each mechanism, regardless of just one symptom category. The scales evaluated in ASD gain importance in this context. Therefore, in order to better evaluate the role of blood parameters evaluated in the study in the etiopathogenesis of ASD and to better understand their relationship with the total scale scores and subscale scores indicating ASD symptom severity, further studies with a larger sample that evaluate blood biochemistry as well as cerebrospinal fluid (CSF) biochemistry are needed.