Axon structure may be different shape than assumed, study finds
Interfering with formation of pearl-like structures impairs signal transmission
Axons, nerve cell projections that carry electrical signals from one cell to another, may look more like pearls on a string than the cylindrical tubes they are commonly believed to resemble, according to a study, which demonstrated that interfering with the formation of pearl-like structures impaired the transmission of electric signals.
Axon pearling is a well-characterized phenomenon that occurs in neurons under stress, including degenerating neurons in neurological conditions like Parkinson’s disease. People with Parkinson’s also show changes in brain signaling.
“Understanding the structure of axons is important for understanding brain cell signaling,” Shigeki Watanabe, PhD, a professor at Johns Hopkins University School of Medicine and senior author of the study, said in a university news story. “Axons are the cables that connect our brain tissue, enabling learning, memory and other functions.”
The results were described in the study, “Membrane mechanics dictate axonal pearls-on-a-string morphology and function,” published in Nature Neuroscience.
For decades, researchers have assumed axons had a cylindrical shape with a constant diameter, containing bubble-like structures with neurotransmitters, signaling molecules that nerve cells (neurons) use to communicate. It was known that pearl-like structures may form in neurons from people with Parkinson’s disease and other neurodegenerative conditions due to the loss of cellular integrity.
Axon structure visualized
Here, researchers used high-pressure freezing electron microscopy to visualize axons, structures about 100 times thinner than human hair. Electron microscopy works by shooting beams of electrons to reveal cell structure.
“To see nanoscale structures with standard electron microscopy, we fix and dehydrate the tissues, but freezing them retains their shape — similar to freezing a grape rather than dehydrating it into a raisin,” Watanabe said.
The researchers used this technique to study mouse neurons grown in a lab, as well as neurons taken from adult mice or from mouse embryos. Neurons were not myelinated, meaning they did not have the myelin sheath that protects axons and facilitates nerve cell communication.
Results showed that pearl-like structures, which the scientists called non-synaptic varicosities, were present in all images taken from brain tissue samples at physiological, or non-disease, conditions. The tiny pearls, about 200 nanometers in diameter, appeared repeatedly along the axons, mixed with thin tube connectors 60 nm in diameter, like pearls on a string.
The scientists found that interfering with the neuronal membrane by increasing the concentration of sugars around the axon or by removing cholesterol from the neuron’s membrane to make it less stiff reduced the formation of pearl-like structures and the pearl structures’ size.
The researchers said the data suggest “that nanopearling is a prominent feature of unmyelinated axons,” and that “membrane mechanics may be a key driver of axon nanopearling.”
Interfering with certain components of the cytoskeleton, the network of protein filaments that serve as a scaffold that determines nerve cell shape, affected connector length and width, the researchers found. “Together, these results suggest that the cytoskeleton contributes to nanopearling by determining the connector dimensions,” they wrote.
When high-frequency electric stimulation was applied to mouse neurons, the pearl-like structures increased by a mean of 8% in length and 17% in width, as did the speed at which electric signals were transmitted. This effect in signal transmission was lost when the researchers interfered with membrane structure by removing cholesterol. “A wider space in the axons allows ions [chemical particles] to pass through more quickly and avoid traffic jams,” Watanabe said.
The research team plans to examine axon structures in brain tissue taken with permission from people having brain surgery and those who have died from neurodegenerative diseases.
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