Schwann cells
Protectors of the nerves
Credit: Art by Nelly Aghekyan. Set in motion by Dr. Emanuele Petretto. Words by Dr. Agnieszka Szmitkowska. Project coordination: Dr. Masia Maksymowicz. Series Director: @Radhika Patnala Sci-illustrate Endosymbiont
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Where biology meets physics
Our nervous system uses both electrical charges and chemicals to send signals between neurons. Neurons, just like tiny electric cables, need insulation to send the signals efficiently, safely, and fast right where they should go. This is where Schwann cells come to shine.
The protective sheath
The Schwann cells were named after German physiologist Theodor Schwann, who discovered them in the 19th century. They are a variety of glial cells (non-neuronal cells) of the peripheral nervous system (PNS), which can produce a fatty substance called myelin (1). Schwann cells can be separated into two categories: myelinating and non-myelinating (2).
The myelinating Schwann cells tightly wrap around the nerve fibres in a spiral manner and form what is called a myelin sheath around the axons of the nerves. The lipid-rich myelin acts as an insulator, ensuring rapid and efficient transmission of electrical signals along the nerve. It also protects the nerves from physical damage and cross-talk with other nerves (3).
On the contrary, the non-myelinating Schwann cells do not form spiral myelin sheaths but support smaller nerve fibres by enveloping multiple nerve fibres simultaneously, just like the main insulation of every multi-conductor cable (4).
The jumping impulses
The Schwann cells do not create one long tube around the neuron’s axon. Instead, each cell myelinates a single segment of the nerve fibre, leaving little gaps called the nodes of Ranvier (5). These nodes play a crucial role in a process called saltatory conduction, where nerve impulses jump from one node to the next, substantially speeding up transmission. This conduction’s “jumping” nature means that the electrical signal can bypass large sections of the axon, allowing it to travel much faster than it would in an unmyelinated axon (6).
Saltatory conduction in myelinated neurons is also more energy-efficient due to the insulating properties of the myelin sheath, which prevents ion leakage. Voltage-gated ion channels are concentrated at the nodes of Ranvier, reducing the number of ions crossing the axon membrane. This localised ionic movement means less energy is spent restoring ion gradients via the sodium-potassium pump. Consequently, myelinated axons achieve rapid signal transmission with lower metabolic demand than unmyelinated ones (7).
When the myelin malfunctions
Dysfunction or anomalies of Schwann cells can lead to a spectrum of neurological disorders such as schwannomas. These are benign tumours originating from Schwann cells. While typically non-malignant, their presence can exert pressure on adjacent structures, leading to neurological deficits (8).
Another condition where Schwann cells are impacted is the Guillain-Barré Syndrome (GBS). GBS is an autoimmune disorder where the body’s immune system mistakenly attacks the peripheral nerves. The myelin sheath produced by Schwann cells is damaged, leading to rapid-onset muscle weakness and sometimes paralysis (9).
Schwann cells to the rescue!
Schwann cells are not only protective, but they also repair (10). They can clear the debris left after injury thanks to a process called phagocytosis (11). Schwann cells can also proliferate and align themselves in columns, forming structures known as the bands of Büngner. These bands serve as a guide or pathway for the regrowing axons, ensuring they reach their original target tissues(12).
That is not all. Schwann cells secrete various growth factors and cytokines that promote nerve regeneration. And, of course, when the nerve regenerates, Schwann cells wrap around the new axons, forming a new myelin sheath. This regenerative capability is limited and decreases with the distance of the injury from the target, but it is a feature that distinguishes the PNS from the CNS, where regeneration is much more limited (13).
The less potential of CNS regeneration is also connected with myelin. Myelin is produced in CNS, too, by cells called oligodendrocytes, which we covered in the previous post. This myelin contains molecules that inhibit axon growth, whereas the myelin produced by Schwann cells in the PNS does not have these inhibitory molecules. For instance, molecules like Nogo, MAG (myelin-associated glycoprotein), and OMgp (oligodendrocyte myelin glycoprotein) in the CNS myelin actively inhibit axonal growth (14).
Due to those features, Schwann cells have been explored as candidates for cell transplantation, especially in spinal cord injuries and peripheral nerve injuries, giving promising results (15).
Recognising and appreciating the labs working in this space:
1. Nancy Ratner’s Lab:Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, United States, https://www.cincinnatichildrens.org/research/divisions/e/ex-hem/labs/ratner
2. Deng’s Lab: Indiana University School of Medicine, United States, https://medicine.iu.edu/faculty-labs/deng-lab
3. The Laboratory of Kristjan R Jessen and Rhona Mirsky, Ucl Research Department Of Cell And Developmental Biology, University College London, UK, https://www.ucl.ac.uk/jessenmirsky/
4. Department of Neuroscience, Baylor College of Medicine, Houston, TX, USA. https://www.bcm.edu/departments/neuroscience
5. Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot, Israel. https://www.weizmann.ac.il/mcb/
6. Department of Axonal Signalling, Netherlands Institute for Neuroscience, Royal Netherlands Academy for Arts and Sciences, Amsterdam, the Netherlands; https://cellbiology.science.uu.nl/research-groups/maarten-kole-axonal-signalling/
7. Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Göttingen, Germany; https://www.mpinat.mpg.de/nave
8. Center for Brain Injury and Repair, Department of Neurosurgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States, https://www.med.upenn.edu/cbir/
9. Center for Neurotrauma, Neurodegeneration and Restoration, Corporal Michael J. Crescenz Veterans Affairs Medical Center, Philadelphia, United States, https://www.va.gov/philadelphia-health-care/research/
10. Department of Medical Biotechnology, School of Advanced Technologies, Shahrekord University of Medical Sciences, Shahrekord, Iran. https://www.skums.ac.ir/Medical-Biotechnology
References
1. Boullerne AI. The history of myelin. Experimental neurology. 2016;283:431–45.
2. Monk KR, Feltri ML, Taveggia C. New insights on Schwann cell development. Glia. 2015;63(8):1376–93.
3. Salzer JL. Schwann cell myelination. Cold Spring Harbor perspectives in biology. 2015;7(8):a020529.
4. Griffin JW, Thompson WJ. Biology and pathology of nonmyelinating Schwann cells. Glia. 2008;56(14):1518–31.
5. Rasband MN, Peles E. Mechanisms of node of Ranvier assembly. Nature Reviews Neuroscience. 2021;22(1):7–20.
6. Cohen CC, Popovic MA, Klooster J, Weil M-T, Möbius W, Nave K-A, et al. Saltatory conduction along myelinated axons involves a periaxonal nanocircuit. Cell. 2020;180(2):311–22. e15.
7. Shimba K, Asahina T, Sakai K, Kotani K, Jimbo Y. Recording saltatory conduction along sensory axons using a high-density microelectrode array. Frontiers in Neuroscience. 2022;16:854637.
8. Hilton DA, Hanemann CO. Schwannomas and their pathogenesis. Brain pathology. 2014;24(3):205–20.
9. Willison HJ, Jacobs BC, van Doorn PA. Guillain-barre syndrome. The Lancet. 2016;388(10045):717–27.
10. Bhatheja K, Field J. Schwann cells: origins and role in axonal maintenance and regeneration. The international journal of biochemistry & cell biology. 2006;38(12):1995–9.
11. Brosius Lutz A, Chung W-S, Sloan SA, Carson GA, Zhou L, Lovelett E, et al. Schwann cells use TAM receptor-mediated phagocytosis in addition to autophagy to clear myelin in a mouse model of nerve injury. Proceedings of the National Academy of Sciences. 2017;114(38):E8072-E80.
12. Panzer KV, Burrell JC, Helm KV, Purvis EM, Zhang Q, Le AD, et al. Tissue engineered bands of büngner for accelerated motor and sensory axonal outgrowth. Frontiers in Bioengineering and Biotechnology. 2020;8:580654.
13. Momenzadeh S, Jami M-S. Remyelination in PNS and CNS: current and upcoming cellular and molecular strategies to treat disabling neuropathies. Molecular Biology Reports. 2021;48(12):8097–110.
14. Giger RJ, Venkatesh K, Chivatakarn O, Raiker SJ, Robak L, Hofer T, et al. Mechanisms of CNS myelin inhibition: evidence for distinct and neuronal cell type specific receptor systems. Restorative neurology and neuroscience. 2008;26(2–3):97–115.
15. Hood B, Levene HB, Levi AD. Transplantation of autologous Schwann cells for the repair of segmental peripheral nerve defects. Neurosurgical focus. 2009;26(2):E4.
About the author:
DR. AGA SZMITKOWSKA
Content Editor The League of Extraordinary Celltypes, Sci-Illustrate Stories
Aga did her Ph.D. in Biochemistry at the CEITEC/Masaryk University in Brno, Czech Republic, where she was a part of the Laboratory of Genomics and Proteomics of Plant Systems. She is a passionate public speaker and science communicator. After graduation, she became a freelance content coordinator and strategist in a start-up environment focused on lifestyle and longevity.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Celltypes, Sci-Illustrate Stories
Nelli Aghekyan, did Bachelor’s and Master’s degrees in Architecture in Armenia; after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Celltypes, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behaviour of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualisation, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Celltypes
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