Social Isolation Disrupts Brain's 'White Matter' Formation – Key to Brain 'Plasticity', MS and Mood Disorders

There are three general types of brain tissue: gray matter (the dendrite component of neurons), white matter (the myelin-coated, axon component of neurons) and glial matter (crucial cells that “support”, protect and nourish these neurons).

The experience of interacting with our environment can trigger changes in brain cells that impact what is known as brain plasticity which is a measure of how well our brain cells adapt to environmental changes. But much of what determines this plasticity remains a mystery. For example, it was thought that only the brain’s  neurons changed in response to alterations in environmental conditions.

But new research by neuroscientists (Dietz and Liu) at the University at Buffalo and Mt. Sinai School of Medicine has revealed that certain types of glial cells — known as oilgodendrocytes — also play a critical role in brain plasticity. Under normal environmental conditions, these glial cells produce myelin, the fatty, whitish protein that coats a neuron’s axon and which permits brain impulses to be conducted across the cell.

But the recent experiments with adult mice have revealed that social isolation triggers disruption in the formation of  the myelin sheaths that envelop the neurons’ axons. This disruption occurred primarily in the prefrontal cortex — a  brain region critical for normal cognitive  and emotional functioning.

Adult mice were socially isolated for an eight week period to “induce a depressive-like state.” The isolated mice were then introduced to a “novel” mouse (a mouse they had not seen previously). The isolated mice failed to interact with the new mouse (note: mice are instinctively social creatures) which was interpreted as a model of social avoidance and withdrawal.

Follow up analysis of the isolated mice brain tissue revealed that levels of gene transcription for oligodendrocytes was significantly reduced in the prefrontal cortex

The experiments revealed that social isolation produces stresses which in turn disrupt the sequence in which the white matter-making cells are formed.

grey and white matter micrograph (by Nephron)
Micrograph showing white matter with its characteristic fine meshwork-like appearance (left of image – lighter shade of pink) and grey matter, with the characteristic neuronal cell bodies


Previous research had linked changes in the brain’s white matter (myelin) to psychiatric disorders including depression. Demyelination — the loss of normal nerve function — has also been linked to multiple sclerosis (MS) and Krabbe’s disease, a rare and fatal childhood disease. And more recently, myelin alterations were observed in young and adolescent mice in response to certain environmental changes. But the exact mechanism that produces this alteration was unclear.

According to lead researcher Karen Dietz: “This research reveals for the first time a role for myelin in adult psychiatric disorders. It demonstrates that plasticity in the brain is not restricted to neurons, but actively occurs in glial cells, such as the oligodendrocytes, which produce myelin.”

The researchers further noted that the key change in the prefrontal cortex lay within the cellular nuclei: there was less of a tightly-packed form of DNA known as heterochromatin. As oligodendrocytes mature, their DNA structure becomes more compacted. This state signals that the cell is mature and ready to produce myelin. But crucial (social) changes in environmental conditions, apparently, can result in less compaction.

Dietz explains: “This process of DNA compaction is what signifies that the oligodendrocytes have matured, allowing them to produce normal amounts of myelin. We have observed in socially isolated animals that there isn’t as much compaction, and the oligodendrocytes look more immature. As adults age, normally, you would see more compaction, but when social isolation interferes, there’s less compaction and therefore, less myelin being made.”

The good news from this research is that the impairment from social isolation is not (at least in adult mice) permanent; after a period of “social reintegration” myelin production levels returned to normal.*

This research not only underscores the deeply intertwined nature of one’s environment and genes, but also indicates that “environmental intervention” can reverse the impacts of social isolation in adults. It is anticipated that this research will open new investigative paths for mood and myelin disorder studies.

It may also offer some hope for MS patients. Says Dietz:

“This research suggests that maybe recovery from an MS episode might be enhanced by social interaction.”

The research report was published in the journal Nature Neuroscience online.

Major funding for the research came from the National Institutes of Health.

* Similar studies on mice by Makinoden et al (2012) “show that mice isolated for 2 weeks immediately after weaning have alterations in prefrontal cortex function and myelination that do not recover with reintroduction into a social environment.” [Science, 14 Sept., 2012, pgs. 1357-60

Quotes source: Univ. of Buffalo press release New form of brain plasticity: Study shows how social isolation disrupts myelin production.

Top Image: (Mood disorder) Idontknowtheworldtoday ; CC – By – SA 3.0

Bottom image: (grey/white matter micrograph); Nephron ; CC – By – SA 3.0

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