A recent publication from a team at Washington University School of Medicine in St. Louis looked at the activity-dependent translational response from astrocytes, using CompBio™ to make novel connections.

 

Previous studies have shown that astrocytes have an activity-dependent transcriptional response and neurons are known to have an activity-dependent transcriptional and translational response. This study aims to find the activity-dependent translation response from astrocytes. Additionally, they addressed whether the astrocyte response depended on neuronal activity. Here, they were able to uncover the translational targets that were promoted in response to activity as well as find that neuronal activity was necessary for this response. Both CompBio and gene ontology (GO) analyses found pathways related to cytoskeleton, ribosomes and mitochondria. The authors note that these pathways suggest the astrocytes are poised by the neuronal activity to have increased perisynaptic process motility. Additionally, CompBio identified genes associated with autism and neurodegenerative disorders. 

 

While the cytoskeleton and energetic changes could be predicted in astrocytes based on the activity of astrocytes after neuronal activation, the connection between neuronal activity and the upregulation of astrocytic genes associated with neurological disorders was previously unknown. The authors found this novel connection through CompBio and were able to support this by independently investigating CompBio-identified literature connections. CompBio analysis also helped uncover the downstream effects of the activation (MAPK and Ras/raf signaling) leading to a more holistic view of the phenomena studied. With the additional finding of the connections to genes altered in Autism Spectrum Disorders (ASDs) and neurodegenerative disorders, they may have uncovered a mechanism that astrocytes may be involved in such disorders, though additional studies are required.

 

 Key takeaways:

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1. CompBio reproduced the GO analysis. Both CompBio and GO analysis found pathways related to cytoskeleton, ribosomes and mitochondria. The authors note that these pathways suggest the astrocytes are poised by the neuronal activity to have increased perisynaptic process motility.

2. CompBio found things that GO missed. CompBio identified genes associated with autism and neurodegenerative disorders in a non-obvious manner not identified by previous tools.