Brain’s ‘wiring insulation’ is one of the major factors of age-related brain deterioration

A new study led by the University of Portsmouth has identified that one of

the major factors of age-related brain deterioration is the loss of a substance

called myelin.

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

aging, which reduces the cell's ability to replace lost myelin.

The study, published this week in the journal Aging Cell, is part of  

an international collaboration led by Professor Arthur Butt at the University of

Portsmouth with Dr. Kasum Azim at the University of Dusseldorf in Germany,

together with Italian research groups of Professor Maria Pia Abbracchio in

Milan and Dr. Andrea Rivera in Padua.

Professor Butt said: “Everyone is familiar with the brain’s grey matter, but

very few know about the white matter, which comprises the insulated

electrical wires that connect all the different parts of our brains.

“A key feature of the aging 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 aging brain.”

By improving our understanding of aging brain stem cells, it gives

us a new target to help slow the progression of MS, and could have

important implications for future treatment.

Dr. Emma Gray, Assistant Director of Research at the MS Society

Dr. Rivera, lead author of the study while he was in the University of Portsmouth

and who is now a Fellow at the University of Padua, explained: “By

comparing the genome of a young mouse brain to that of a senile mouse, we

identified which processes are affected by aging. These very sophisticated

analysis allowed us to unravel the reasons why the replenishment of

oligodendrocytes and the myelin they produce is reduced in the aging

brain.

“We identified GPR17, the gene associated to these specific precursors, as

the most affected gene in the aging 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 aging 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 specialized brain stem cells Oligodendrocyte

Progenitor Cells (OPCs) in the grey and white matter of the brain. 

Credit: Dr. Andrea Rivera

Dr. Rivera performed the key experiments published in this study while at the

University of Portsmouth and he has been awarded the prestigious MSCA

Seal of Excellence @UniPD Fellowship to translate these findings and

investigate this further in the human brain, in collaboration with Professors

Raffele De Caro, Andrea Porzionato and Veronica Macchi at the Institute of

Human Anatomy of the University of Padua.

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 Ph.D. 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 becomes less efficient as we age, and we’re really proud to have helped

fund it. By improving our understanding of aging brain stem cells, it gives

us a new target to help slow the progression of MS, and could have

important implications for future treatment.”