Brain’s ‘wiring insulation’ is one of the major factors of age-related brain deterioration
Myelin acts like the protective and insulating plastic casing around the electrical wires of the brain - called axons. Myelin is essential for superfast communication between nerve cells that lie behind the supercomputer power of the human brain.
The loss of myelin results in cognitive decline and is central to several neurodegenerative diseases, such as Multiple Sclerosis and Alzheimer’s disease. This new study found that the cells that drive myelin repair become less efficient as we age and identified a key gene that is most affected by ageing, which reduces the cells ability to replace lost myelin.
Everyone is familiar with the brain’s grey matter, but very few know about the white matter, which comprises of the insulated electrical wires that connect all the different parts of our brains.
Professor Butt said: “Everyone is familiar with the brain’s grey matter, but very few know about the white matter, which comprises of the insulated electrical wires that connect all the different parts of our brains.
“A key feature of the ageing brain is the progressive loss of white matter and myelin, but the reasons behind these processes are largely unknown. The brain cells that produce myelin - called oligodendrocytes – need to be replaced throughout life by stem cells called oligodendrocyte precursors. If this fails, then there is a loss of myelin and white matter, resulting in devastating effects on brain function and cognitive decline. An exciting new finding of our study is that we have uncovered one of the reasons that this process is slowed down in the ageing brain.”
By improving our understanding of ageing brain stem cells, it gives us a new target to help slow the progression of MS, and could have important implications for future treatment.
“We identified GPR17, the gene associated to these specific precursors, as the most affected gene in the ageing brain and that the loss of GPR17 is associated to a reduced ability of these precursors to actively work to replace the lost myelin.”
The work is still very much ongoing and has paved the way for new studies on how to induce the ‘rejuvenation’ of oligodendrocyte precursor cells to efficiently replenish lost white matter.
Dr Azim of the University of Dusseldorf said: “This approach is promising for targeting myelin loss in the ageing brain and demyelination diseases, including Multiple Sclerosis, Alzheimer’s disease and neuropsychiatric disorders. Indeed, we have only touched the tip of the iceberg and future investigation from our research groups aim to bring our findings into human translational settings.”
The image shows myelin and specialised brain stem cells Oligodendrocyte Progenitor Cells (OPCs) in the grey and white matter of the brain. Credit: Dr Andrea Rivera
The study was funded by grants from the BBSRC and MRC to Professor Butt, together with the UK and Italian MS Societies (to Professors Butt and Abbracchio, respectively), and the Swiss National Funds Fellowship and German Research Council (Dr Azim). Dr Andrea Rivera was supported by an Anatomical Society PhD Studentship (with Professor Butt), and the MSCA Seal of Excellence @UniPD (Dr Rivera).
Dr Emma Gray, Assistant Director of Research at the MS Society, said: “MS can be relentless and painful, and there are sadly still no treatments to stop disability progression. We can see a future where no one has to worry about MS getting worse but, for that to happen, we need to find ways to repair damaged myelin. This research sheds light on why cells that drive myelin repair become less efficient as we age, and we’re really proud to have helped fund it. By improving our understanding of ageing brain stem cells, it gives us a new target to help slow the progression of MS, and could have important implications for future treatment.”