The Use of Synaptosomes in Studying Autism Spectrum Disorder and Other Neurodevelopmental Disorders Chapter uri icon

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abstract

  • Autism spectrum disorder (ASD) is one of the most common neurodevelopmental disorders in children. Atypical neural connectivity and signalling are major contributors behind the pathology of ASD and genome sequencing studies of individuals affected by ASD have revealed the association of synaptic proteins to the disorder. By studying synaptosomes isolated from human or mouse tissue, it is possible to study the role of proteins on synaptic function and localization. We have shown that Dixdc1 and Mark1 localization in the synapse is important for its function in synapse formation through actin polymerization. However, further study of Dixdc1 and other ASD-associated genes requires the generation of newer mouse models that recapitulate the genetic disruptions seen in humans or by studying the genes in a human context and more broad methods of studying the synaptic protein networks involved. The CRISPR/Cas9 genome editing system offers an efficient and easier method of creating ASD mouse models or human IPSC-derived neuron models to study the effect on the synaptic compartment. The generation of brain organoids further advances the capability of studying synaptic formation and function in a human context at an early developmental time point. Lastly, the use of BioID allows tagging of even transient protein interactions that can be used to identify disruptions in synaptic protein networks through proteomic analysis. Overall, the use of synaptosomes is widely important in studying the mechanisms involved in the development of ASD, which is linked with atypical synaptic formation and function.

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publication date

  • 2018