Understanding oligodendrocyte turnover

Dr Kaylene Young

Menzies Institute for Medical Research, TAS

| A cure via repair and regeneration | Neurobiology | Project | 2012 | Investigator Led Research |
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Summary

Dr Kaylene Young and her colleagues are investigating the biology of oligodendrocytes, the myelin forming cells in the brain. She will investigate how these cells function and whether they can be stimulated to overcome the limitations to myelin repair that exist in MS.

The successful conduction of the electrical impulses in nerves, relies on the nerve cells being insulated like electrical cables. This insulation, called myelin, also protects and supports the nerve cell. In MS this insulation is lost, causing a block in conduction and making the nerve cells vulnerable to damage. Although myelin is repaired in MS, this repair is often incomplete, contributing to the ongoing disability seen in this disease.

Dr Young and her colleagues recently discovered that a specialised type of cell in the brain, known as an oligodendrocyte progenitor cell (OPC) makes new oligodendrocytes throughout life. The team has then investigated how OPCs make new insulating cells in the normal central nervous system, and how this differs under disease conditions in laboratory models of MS.

As OPCs are found in all regions of our central nervous system, targeting OPCs to make more insulating cells to prevent nerve damage could provide a novel therapeutic approach to enhance myelin repair in the brain and spinal cord to treat MS.

This project brings together a team of highly talented young researchers who are forging their independent careers in MS research with the support of the exceptional MS research hubs at the University of Melbourne and the Menzies Institute for Medical Research.

References

  • Young K.M, Psachoulia K, Tripathi RB, Dunn S, Cossell L, Attwell DA, Tohyama K and Richardson WD. (2013) Oligodendrocyte dynamics in the healthy adult CNS: evidence for myelin remodelling. Neuron 77: 873-885.
  • Koenning M, Jackson S, Hay CM, Faux C, Kilpatrick TJ, Willingham M, Emery B. (2012) Myelin gene regulatory factor is required for maintenance of myelin and mature oligodendrocyte identity in the adult CNS. J Neurosci. 32: 12528-42.
  • Wang S and Young K.M. (2013). White matter plasticity in adulthood. Neuroscience pii: S0306-4522(13)00871-3. doi: 10.1016/j.neuroscience.2013.10.018
  • Young, K.M. (2013). Stem cells short-circuit nerve diseases. Australasian Science. 34(9), 32.

Project Outcomes

In the first stage of analysis, the team found that the myelin insulation that is laid down by oligodendrocytes generated during adulthood is thinner and the segments are much shorter than that produced by oligodendrocytes generated during development. This is highly reminiscent of the insulation that is generated as part of lesion repair during MS. Therefore, this indicates that the ‘abnormal’ insulation that has long been associated with repair (such as myelin characterised by thinner, shorter insulation segments) is actually a feature of the insulation made by oligodendrocytes generated during normal adulthood.

This was previously thought to be a pathological feature of multiple sclerosis because it is most clearly visible when the short, thin myelin segments are laid down together as occurs at a lesion site. In the normal adult central nervous system, these myelin segments are being added, but they are highly distributed. This experiment showed that this adult insulation is good enough to support nerve cells and information transfer, suggesting that future research into therapeutic intervention should focus on targeting the OPCs to increase the number of new oligodendrocytes available to protect nerve cells, rather than trying to improve the insulation-process itself.

Subsequent work revealed that oligodendrocytes do die within the normal adult CNS. This has been a point of uncertainty for many years, with researchers indicating that oligodendrocyte turnover maybe a normal process, but being unable to prove or disprove this idea. The team have found that oligodendrocytes don’t only die during multiple sclerosis, but that a large number of oligodendrocytes die throughout life.

Importantly, Dr Young and her colleagues then showed that oligodendrocyte death is outweighed by oligodendrocyte birth, so that across the lifetime there is net gain in the number of cells. This suggests that new oligodendrocytes play multiple different roles in the adult nervous system, and are capable of efficiently replacing oligodendrocytes that die, and perhaps even adding insulation to regions that were not insulated previously.

This research indicates that many of the processes observed to occur in multiple sclerosis occur in the normal brain, but to a lesser extent. However, understanding the normal process of successful and effective oligodendrocyte turnover may provide critical clues for enhancing nervous system repair.

Updated: 30 June 2014

Updated: 06 January, 2012

Investigator

  • Dr Kaylene Young, Menzies Institute for Medical Research, The University of Tasmania, TAS
  • Dr Ben Emery, Centre for Neuroscience, The University of Melbourne, VIC
  • Dr Tobias Merson, Florey Neuroscience Institutes, The University of Melbourne, VIC

Grant Awarded

  • Project Grant

Total Funding

  • $180,000

Duration

  • 2 years over 2012 - 2013

Funding Partner

  • Foundation 5 Million
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