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Gene linked to myelin repair in the brain

Scientists have identified a genetic repair process in the brain that can re-coat nerves with myelin – fatty ‘insulation’ – that is stripped away in multiple sclerosis. In a study published in the December 17 issue of the journal Science, scientists from the Centre for Brain Repair and the School of Veterinary Medicine at the University of Cambridge and the Dana-Farber Institute at Harvard University, report that the gene Olig 1, thought to aid the development of certain brain cells, is essential for the myelin-repairing process in adults with Central Nervous System (CNS) diseases like Multiple Sclerosis (MS).

From University of Cambridge :
Gene linked to myelin repair in the brain

Scientists have identified a genetic repair process in the brain that can re-coat nerves with myelin – fatty ‘insulation’ – that is stripped away in multiple sclerosis.

In a study published in the December 17 issue of the journal Science, scientists from the Centre for Brain Repair and the School of Veterinary Medicine at the University of Cambridge and the Dana-Farber Institute at Harvard University, report that the gene Olig 1, thought to aid the development of certain brain cells, is essential for the myelin-repairing process in adults with Central Nervous System (CNS) diseases like Multiple Sclerosis (MS).

Affecting about two and half million people worldwide, MS is an inflammatory disease of the CNS and one of the most common causes of neurological disability in young adults. Symptoms of the disease range from fatigue and numbness to difficulties with memory, speech and movement and alternately worsen and improve in an unpredictable ‘relapsing/remitting’ pattern. During remissions, randomly damaged nerves in the brain and spinal cord become recovered with myelin, a fatty substance forming the insulating sheath around long, threadlike nerve cells that transmit signals in the form of electrical impulses.

Working with tissue from rodents and humans, the researchers determined that the Olig 1 gene jump-starts a process that can restore, at least temporarily, the myelin coating of nerves damaged in MS.

The two teams headed by Drs Charles Stiles and David Rowitch in Boston and Dr Robin Franklin in Cambridge, investigated the role of the Olig 1 gene. When Olig1 and its close relative Olig2 were initially identified, it appeared that Olig2 was required for the fetal development of oligodendrocytes (cells that provide the myelin to wrap nerves in the CNS) while the role of the Olig 1 gene was not determined.

In order to identify the role of the Olig 1 gene, the two teams used antibodies to highlight the location of the proteins encoded by Olig 1 and 2 in brain cells from embryonic and adult mice. While in embryonic cells both proteins were located in the nucleus, as anticipated since their role is to regulate expression of other genes that produce the myelinating cells, in adult cells the Olig 1 protein had migrated to the cytoplasm outside the nucleus, where there are no genes to regulate.

Looking for the location of Olig 1 in adult rodents with a demyelinating injury, however, the researchers found that Olig 1 would appear in the nucleus. That is, following an injury the brain cells had in effect reverted to a fetal state in which Olig 1 could trigger the formation of new oligodendrocytes.

Furthermore, when the researchers induced demyelinating lesions in Olig 1 ‘knockout mice’ that could not produce the Olig 1 protein, they found that although brain developed normally it could not repair the demyelinating lesions.

Together with Dr Cedric Raine from the Albert Einstein College of Medicine in New York, the scientists used post mortem brain tissue from MS patients to pinpoint the location of Olig 1 in the human samples. In the healthy areas of the brain, the Olig1 gene appeared inactive while in damaged regions it was active, and possibly contributing to the formation of new oligodendrocytes.

“This suggests that the Olig 1’s function has been shaped by evolution to repair the brain in areas where the insulating layer of myelin has been depleted through disease,”
said Dr Franklin, lead investigator of the Cambridge Centre for Brain Repair team.

While the cycle of damage and repair can go on for many years in MS patients, eventually the system wears down, and in most people the disease progresses with fewer remissions.

“Perhaps the signal that calls Olig 1 into service becomes weaker,”
said Dr Stiles lead investigator of the Dana-Faber Institute team.

“Although this finding will not yield direct results in terms of finding treatment for MS we are confident that it gives new insight and direction for research.”
The researchers conclude that although MS may not be completely preventable, there is hope that therapeutic approaches, focusing on the repair process will be available in the future.




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