Demyelination ages the brain
A new study conducted by the University of Portsmouth, UK, has shown that one of the main factors of age-related deterioration of the brain is the loss of myelin.
Myelin is a protective insulating sheath around nerve fibers. It is necessary for ultrafast communication between nerve cells.
The loss of myelin leads to a decrease in cognitive functions and is a key pathogenetic link in some neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease. In a new study led by Professor Arthur Butt, it was shown that the cells that are responsible for restoring myelin become less active with age. A gene responsible for the age-related decrease in the ability of cells to restore lost myelin was also identified.
Myelin (blue) and specialized brain stem cells are the progenitor cells of oligodendrocytes (pink) in the gray and white matter of the brain.
A key feature of the aging brain is the progressive loss of white matter and myelin, but the causes of these processes are largely unknown. In the brain, myelin is produced by oligodendrocytes. Throughout life, non-functioning oligodendrocytes are replaced by new ones created from progenitor cells. Without this, there is a loss of myelin and white matter, leading to devastating consequences for brain function and cognitive decline.
By comparing the brain genomes of young and old mice, the research team determined which processes are affected by aging. This complex analysis allowed us to find out the reasons for the decrease in the number of oligodendrocytes and the myelin produced by them in the aging brain.
The researchers identified the GPR17 gene, which was associated with the loss of myelin in the aging brain; inhibition of GPR17 was associated with a reduced ability of oligodendrocyte precursors to turn into oligodendrocytes.
The group also searched for small molecules capable of rejuvenating the progenitor cells of oligodendrocytes. The most promising was the LY294002 compound, which affects the mTOR signaling pathway. Mice at the age of 6 months, when the aging processes of the brain are already starting, were intraventrically injected with LY294002. It was found that the number of oligodendrocyte progenitor cells and the myelination index in their brains on day 14 after injection were significantly higher than in control mice
Currently, researchers continue to work on finding ways to rejuvenate the progenitor cells of oligodendrocytes. This direction is promising for combating the loss of myelin in the aging brain and in demyelinating diseases, including multiple sclerosis, Alzheimer's disease and neuropsychiatric disorders.
Article by A.D.Rivera et al. Functional genomic analyses highlight a shift in Gpr17-regulated cellular processes in oligodendrocyte progenitor cells and underlying myelin dysregulation in the aged mouse cerebrum published in the journal Aging Cell.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of the University of Portsmouth: Brain's 'wiring insulation' as a major factor of age-related brain determination.