Molecular Markers for Glial Cells Identified
One of the major challenges in promoting and restoring the normal function of the nervous system following injuries, diseases, is the inability to distinguish specific glial cells at synapses from the diverse overall population of glial cells. Glial cells are crucial for the formation, repair, and maintenance of synapses throughout the nervous system.
A new study reports that unique cellular and molecular features of glial cells can be revealed by specific labeling of synaptic Schwann cells.
Important molecules to study and to manipulate the specific glial cells integral to synapses have been identified by a team of researchers led by Gregorio Valdez, Ph.D., an associate professor of molecular biology, cell biology, and biochemistry at Brown University.
Presynaptic Schwann cells (PSCs) are non-myelinating, specialized, synaptic glia of the neuromuscular junction (NMJ), that participate in synapse function, development, repair, and maintenance. As the identities of cell-specific PSC molecular markers have remained elusive, an anatomy-based approach was used to study PSCs. The researchers wrote that this limited approach precluded their ability to isolate and genetically manipulate PSCs in a cell-specific manner.
They identified a unique molecular marker of S100β+ PSCs in skeletal muscle, the neuron-glia antigen 2 (NG2). Schwann cells already associated with the NMJ expressed NG2, which indicates that it is a marker of differentiated PSCs. They labeled PSCs in a newly generated transgenic mouse and demonstrated that PSCs have a unique molecular signature that includes genes crucial for PSCs and synapses.
These findings could help to reveal the drivers of PSC differentiation and function. Moreover, it will help to address fundamental questions and speed up the development of therapeutics that can restore the normal function of neurons.
The only cells in muscles expressing two specific molecules are the Schwann cells, a significant subtype of glia located at neuromuscular synapses, the study reveals. And these molecular markers helps to identify the vital cell subtype, providing a highly specific glial “bar code.”
The findings could finally help to figure out how muscle, neuron, and glia cells interact with each other at the synapse. The critical component of the synapse can now be identified using this unique tool.
Neuromuscular diseases such as spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS) can be studied better using this novel bar code. The role of synaptic glia in neuromuscular synapse repair following degeneration during normal aging, the progression of neuromuscular diseases, and injury can now be well studied using the molecular markers.
The synaptic glial cells located at synapses between pairs of neurons in the brain can be revealed by a similar approach.
The same approach can be used to label and target synaptic glial cells in the brain, said Valdez. The discovery could be very helpful in developing treatments for brain conditions like Alzheimer’s Disease.