Comprehensive Summary
This study by Bernou et al. focuses on investigating the function of Brain-Derived Extracellular Vesicles (BDEVs) in neuron networks. Although this has been studied, previous models were limited in their ability to account for the specificities of the human brain. To solve this issue, this study uses a newly developed air-liquid microfluidic platform that injects and collects BDEVs from organotype culture of post-mortem adult human brain explants while measuring electrical activity. Using mass spectrometry, they discovered that BDEVs have large amounts of synaptic proteins, including neural cell adhesion molecules, syntaxin-1A, and synaptopodin. The results of the microfluidic platform showed that injection of BDEVs caused a decrease in local field potential, especially for high frequency oscillations. Additionally, a machine learning framework showed that co-treatment with BDEVs and GW4869 countered the effects of just BDEV. Altogether, these results demonstrate the effects of BDEVs on neural network activity.
Outcomes and Implications
The medical implications of this study are focused on how BDEVs seem to have significant effects on neural network activity, which can be used for therapeutic applications, diagnosing, or for better understanding of the nervous system. BDEVs have the possibility of being used as drug delivery mechanisms. Additionally, studies have shown that they may be used as diagnostic biomarkers for neurodegenerative diseases. Finally, their influence on neural network functioning could provide important insight into synaptic plasticity and neuronal communication in the central nervous system.