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Myelination Exhibits Plasticity, Links to Behavior in Adult Brain

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By Anette Breindl
Science Editor

Multiple sclerosis is perhaps the best known of the demyelinating disorders, where loss of the insulating sheath surrounding neurons makes high-speed communication impossible.

But there are also problems with myelin, although usually to a lesser degree, in other disorders, including traumatic brain injury and some psychiatric diseases such as schizophrenia.

And social isolation, though it does not cause the loss of existing myelin, slows down the formation of new myelin so that animals who are isolated for a period of time ultimately have less myelin than normal.

Such is the conclusion of scientists from the Mount Sinai School of Medicine, who looked at the effects of isolating adult mice on both forebrain myelination and depression-like behaviors.

They published their results in the Nov. 11, 2012, online issue of Nature Neuroscience.

Senior author Patrizia Casaccia stressed that unlike in demyelinating diseases, existing myelin does not disappear during social isolation. "We are not saying that myelin is lost," she told BioWorld Today.

Instead, myelin that would otherwise still be forming in adult brains is never laid down, leading over time to brains that are overall less myelinated in isolated animals than in in those that have had plenty of social interaction.

"We are born with very little myelin," Casaccia said. Myelination proceeds at a rapid pace during the first few years of life. But it continues, to a lesser degree, for decades. "During the third decade of life, new myelin is still being formed."

The impetus to look at social effects, and to do so in adult animals, was twofold. Partly, it came from "discussions we had with patients with multiple sclerosis."

When interacting with patient or advocacy groups, she said, "patients always ask 'Is there anything I can do?'"

There is also a clinical association between multiple sclerosis and depression. And while it is easy to see why someone who is diagnosed with a disabling, progressive and unpredictable demyelinating disorder might become depressed, Casaccia said she thought that myelin problems might also contribute to depression in addition to the symptoms more commonly associated with multiple sclerosis.

In their experiments, Casaccia and her team isolated adult mice, which are normally social animals, for eight weeks. Such isolation induces the mouse equivalent of social withdrawal, which is a symptom of depression in humans.

The team looked at the myelin sheaths in mice that had been isolated, and found that they were overall healthy and able to support neuronal transmission. But they were thinner than the sheaths of mice that had been group-housed throughout their lives.

The animals also showed changes in gene expression, and in their chromatin, DNA's nuclear packaging that can affect gene expression by making DNA more or less accessible to the transcription machinery of the cell.

To truly be a form of plasticity, changes in response to experience need to be reversible, and so Casaccia and her team tested what happened if they reintroduced isolated animals into a social group. They found that after four weeks of group housing, both the social withdrawal symptoms and the gene expression changes were reversed in such animals.

Scientifically, the experiments showed that "an adult brain retains a level of plasticity not only in neurons and in stem cells, but also in myelin." In doing so, they also elucidate why so many progenitors capable of making oligodendrocytes remain in the brain past the time when most myelination is over.

"Five percent of the total cells of the adult brain are glial progenitors," Casaccia said. "And one of the big questions has always been 'Why are they there? Why do we have so many?'"

In a more practical sense, "the bottom line," she said, "is that there is hope for repair by changing our lifestyle."

Additionally, the work itself is "a good start" toward perhaps finding ways to increase myelination via pharmacological means, although beyond the changes to chromatin structure that accompany the myelin changes, the experiments so far have not identified specific targets for doing so.

"We are now trying to understand the molecular mechanisms" that link social interaction to myelin formation, and those molecular mechanisms may identify such targets, Casaccia noted.