Oligodendrocytes
Myelinating cells of the central nervous system
Credit: Art by Sam Esquillon. Set in motion by Dr. Emanuele Petretto. Words by Dr. Masia Maksymowicz. Project Coordinator: Dr. Masia Maksymowicz, Series Director: Dr. Radhika Patnala Sci-illustrate Endosymbiont
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ERRATUM: From our knowledge, the current version of this figure and animation might be getting two things wrong:
1. Axo-axonic and dendro-dendritic synapses, although existing in specialized cell types and brain regions, may not occur together in the same neuron type.
2. Even though retrograde signaling in neurons exists, it may not be the norm, especially for action potential, and depicting it the current way in the right side neuron might be confusing.
An updated version of this illustration and animation will be updated in the article soon.
Myelination in the central nervous system
The final glial cells that we will discuss in this series are oligodendrocytes. Similar to Schwann cells (feature coming soon), they are responsible for myelination (formation of myelin sheath) of the neuronal axons. Mature oligodendrocytes form membrane extensions that wrap around the axon, facilitating rapid and efficient electrical signal transmission between neurons. Still, unlike Schwann cells, which are located in the peripheral nervous system (PNS), oligodendrocytes provide their support in the central nervous system (CNS) (1). Another difference is that a single oligodendrocyte can cover up to 50 axons (2). However, when the myelin sheath is damaged, the electrical impulses are slowed down, resulting in neurological problems. The most well-known disease that targets myelin is multiple sclerosis.
Complex differentiation
To perform their functions, oligodendrocytes go through a very complex differentiation program. It starts with the oligodendrocyte precursor cells/progenitors (OPCs), which originate from the same cell lineage as motor neurons (3). OPCs start migrating across the spinal cord to finally differentiate into myelinating oligodendrocytes. Interestingly, OPCs come in ‘waves’, each having a redundant function. Yet, different OPC populations tend to compete with each other for the space in the developing brain during differentiation (4). In recent years, scientists observed that oligodendrocytes are a heterogenous cell type, which differs both morphologically and functionally depending on multiple factors, such as age, sex, developmental origin, location, and transcription (5). However, it is not understood whether these subtypes are just different, or they get influenced by their microenvironment (5).
Metabolic support and neurodegeneration
Once oligodendrocytes produce the myelin sheath around axons, their gene transcription is changed. Some genes are expressed while others are no longer transcribed. This is needed to maintain the myelin throughout the life via proper regulation of signaling and metabolism (5–6). However, in the context of neurodegeneration, oligodendrocytes play a significant role. The loss of these cells or the integrity of the myelin sheath can have detrimental effects on neuronal function. Conditions like multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), and some forms of dementia involve the breakdown of myelin and the death of oligodendrocytes (6–10). Such disruptions in myelination can lead to slowed or impaired neural communication, contributing to the progressive deterioration of cognitive and motor functions seen in neurodegenerative diseases. Oligodendrocytes are also implicated in numerous psychiatric disorders, e.g. depression (11). Understanding the interactions between oligodendrocytes and neurodegeneration is essential for developing potential therapeutic strategies to halt or mitigate the progression of these debilitating conditions.
Recognizing and appreciating the labs working in this space
- Oligodendrocyte Lab, University of Oslo, Norway, https://www.med.uio.no/imb/english/research/groups/oligodendrocyte-lab/index.html
- Richardson Lab, University College London, UK, https://www.ucl.ac.uk/~ucbzwdr/Richardson.htm
- The Hill Lab, Dartmouth College, USA, https://sites.dartmouth.edu/robert-hill-lab/research/
- The Mayoral Lab, Brown University, USA, https://sites.brown.edu/mayorallab/
- Grinspan Laboratory, Leonard and Madlyn Abramson Pediatric Research Center, Philadelphia, USA, https://www.research.chop.edu/grinspan-laboratory
- Oligodendrocyte & Myelin Research Group, University of Birmingham, UK, https://www.birmingham.ac.uk/research/inflammation-ageing/research/oligo-myelin-research-group/index.aspx
- Center of the Brain Health, University of Birmingham, UK, https://www.birmingham.ac.uk/research/centre-for-human-brain-health/index.aspx , Twitter: @TheCHBH
- The Hinman Lab, UCLA, USA, https://hinmanlab.dgsom.ucla.edu/pages/oligodendrocytes , Twitter: @UCLANeurology
- Neurobiology Lab, University of the Basque Country, Spain, https://www.neurobiologylab.org/research/oligodendrocyte-receptors
- Zuchero Lab, Stanford University, USA, https://zucherolab.stanford.edu/research/, Twitter: @ZucheroLab
References
- Bradl, Monika, and Hans Lassmann. “Oligodendrocytes: biology and pathology.” Acta neuropathologica vol. 119,1 (2010): 37–53. doi:10.1007/s00401–009–0601–5
- Baumann, N, and D Pham-Dinh. “Biology of oligodendrocyte and myelin in the mammalian central nervous system.” Physiological reviews vol. 81,2 (2001): 871–927. doi:10.1152/physrev.2001.81.2.871
- Richardson, W D et al. “Oligodendrocyte lineage and the motor neuron connection.” Glia vol. 29,2 (2000): 136–42. doi:10.1002/(sici)1098–1136(20000115)29:2<136::aid-glia6>3.0.co;2-g
- Kessaris, Nicoletta et al. “Competing waves of oligodendrocytes in the forebrain and postnatal elimination of an embryonic lineage.” Nature neuroscience vol. 9,2 (2006): 173–9. doi:10.1038/nn1620
- Seeker, Luise A, and Anna Williams. “Oligodendroglia heterogeneity in the human central nervous system.” Acta neuropathologica vol. 143,2 (2022): 143–157. doi:10.1007/s00401–021–02390–4
- Philips, Thomas, and Jeffrey D Rothstein. “Oligodendroglia: metabolic supporters of neurons.” The Journal of clinical investigation vol. 127,9 (2017): 3271–3280. doi:10.1172/JCI90610
- Benarroch, Eduardo. “What Is the Role of Oligodendrocytes in Amyotrophic Lateral Sclerosis?.” Neurology vol. 97,16 (2021): 776–779. doi:10.1212/WNL.0000000000012706
- Sams, Eleanor Catherine. “Oligodendrocytes in the aging brain.” Neuronal signaling vol. 5,3 NS20210008. 6 Jul. 2021, doi:10.1042/NS20210008
- López-Muguruza, Eneritz, and Carlos Matute. “Alterations of Oligodendrocyte and Myelin Energy Metabolism in Multiple Sclerosis.” International journal of molecular sciences vol. 24,16 12912. 18 Aug. 2023, doi:10.3390/ijms241612912
- Lee, Youngjin et al. “Oligodendroglia metabolically support axons and contribute to neurodegeneration.” Nature vol. 487,7408 (2012): 443–8. doi:10.1038/nature11314
- Zhou, Butian et al. “Oligodendrocyte lineage cells and depression.” Molecular psychiatry vol. 26,1 (2021): 103–117. doi:10.1038/s41380–020–00930–0
About the author:
DR. MAŁGORZATA ‘MASIA’ MAKSYMOWICZ
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Maksymowicz did her Ph.D. in Cell Biology (IIMCB, Poland) studying the intracellular trafficking and inflammatory signalling of a cytokine receptor. She did a 1-year post-doc at Nencki Institute, Poland, studying the protein- and RNA-binding properties of proteins. Currently, she is doing a post-doc at Barts Cancer Institute, UK, studying the links between endocytosis and tumorigenesis. Dr. Maksymowicz is passionate about science and loves to combine different fields of biology, always trying to seek beauty in nature.
About the artist:
SAM ESQUILLON
Contributing Artist The League of Extraordinary Celltypes, Sci-Illustrate Stories
Sam worked for a couple of educational children’s shows as an illustrator, puppeteer, art director, and production designer. He still works as a production designer for international films and tv/ online streaming shows.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior 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 visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
