A recent study conducted by researchers at Oregon Health & Science University has shed light on the function of a little-known synapse, or junction, between cells in the brain. This discovery could have significant implications for the treatment of various conditions, including multiple sclerosis, Alzheimer’s disease, and glioma, a type of brain cancer.
The researchers focused on the synapse that connects neurons to oligodendrocyte precursor cells (OPCs). OPCs have the ability to differentiate into oligodendrocytes, which produce a protective sheath called myelin around nerves. Myelin plays a crucial role in transmitting electrical signals between cells.
The study found that these synapses play a pivotal role in the production of myelin. This is the first investigation of these synapses in live tissue, providing a better understanding of how these cells work in normal development. In the future, researchers may look at how these synapses function differently in the context of patients with multiple sclerosis.
The existence of these synapses was initially discovered by OHSU researchers at the Vollum Institute in 2000. Prior to this groundbreaking discovery, synapses in the brain were only known to carry neurotransmitters between neurons, making the synapse between neurons and OPCs a revelation.
After two decades, scientists still didn’t fully understand the function of these synapses. To tackle this problem, researchers used single-cell imaging of live tissue in transparent zebrafish, which allowed them to observe the inner workings of the central nervous system in real-time. By using advanced imaging, pharmacology, and gene-editing techniques, they were able to predict the timing and location of myelin formation based on neuron-OPC synapses.
The findings of this study are just the beginning of understanding the importance of these synapses. Oligodendrocyte precursor cells make up about 5% of all brain cells, suggesting that the synapses they form with neurons could be relevant to a wide range of diseases, including the formation of cancerous tumors.
Previous studies have suggested a role for OPCs in neurodegenerative conditions like multiple sclerosis, Alzheimer’s disease, and even psychiatric disorders like schizophrenia. By demonstrating the basic function of the synapse between neurons and OPCs, the study may pave the way for new methods of regulating OPC function to alter disease progression. For example, these synapses could be crucial in promoting remyelination in conditions like multiple sclerosis, where myelin has been degraded, leading to the slowing or blocking of electric signals necessary for various bodily functions.
The discovery of these synapses may also have immediate implications in the field of cancer. In glioma, a type of brain cancer, these synapses are hijacked to drive tumor progression. Modulating the synaptic input involved in tumor formation while still allowing for normal synaptic signaling could be a potential avenue for intervention.
Although only a fraction of OPCs go on to form oligodendrocytes, it is becoming evident that they have other functions aside from myelin formation. The synaptic connection between OPCs and neurons likely plays a fundamental role in the brain, and further exploration is warranted.
The research was conducted by senior author Kelly Monk, Ph.D., professor and co-director of the Vollum Institute at OHSU, lead author Jiaxing Li, Ph.D., a postdoctoral fellow in Monk’s lab, and co-authors Tania Miramontes of OHSU and Tim Czopka, Ph.D., of the Centre for Clinical Brain Sciences at the University of Edinburgh in the U.K.
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