olig 1

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Gene Linked To Myelin Repair In The Brain

12/17/2004

Source: University of Cambridge

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 Stiles and Rowitch in Boston and Dr

Robin lin 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 lin, 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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