A new US study finds that depriving adult mice of social contact reduces production of myelin, the protein sheath that surrounds the fibers or axons that convey electrical signals between nerve cells. The researchers also found socially isolated mice had lower levels of myelin-forming cells in the part of the brain that is important for complex emotion and thinking, and suggest reduced myelin production may play a role in the development of mental illness.
The good news is myelin production appears to be restored once social contact resumes.
Senior investigator Patrizia Casaccia, from the Graduate School of Biomedical Sciences at Mount Sinai School of Medicine in New York, and colleagues, write about their work in the 11 November online issue of Nature Neuroscience.
Casaccia, a professor of neuroscience, genetics and genomics, and also of neurology at Mount Sinai, says in a statement released on Friday:
“We knew that a lack of social interaction early in life impacted myelination in young animals but were unsure if these changes would persist in adulthood.”
“Social isolation of adult mice causes behavioral and structural changes in neurons, but this is the first study to show that it causes myelin dysfunction as well,” she adds.
Myelin is a protein that forms the protective sheath that insulates nerve fibers in the brain, spinal cord and eyes and preserves the vital electrical signals they carry.
In the case of MS, the cause of myelin loss is attack by the immune system, which mistakenly treats the tissue as alien. Another study reported recently in Nature Biotechnology, describes how, using nanoparticles, scientists were able to trick the immune system to stop attacking myelin in mice with MS.
Another way myelin loss occurs is if new myelin production ceases. This is what Casaccia, who is also Chief of the Center of Excellence for Myelin Repair at the Friedman Brain Institute at Mount Sinai, and her team investigated.
New myelin is produced by nerve cells called oligodendrocytes. These work both during development when new nerve cells are being made, and also in adulthood to repair damage, such as that caused by the immune system in people with MS.
Casaccia’s team found after 8 weeks of isolation, adult mice showed signs of social withdrawal.
When they analyzed the mice’s brain tissue and compared it to mice that had not been isolated, the isolated mice had lower levels of myelin-forming oligodendrocytes in the prefrontal cortex, but not in other areas of the brain. The prefrontal cortex is responsible for complex emotional and cognitive behavior.
The team also identified changes in chromatin, the packing material for DNA, which prevented the oligodendrocytes being available for gene expression. (This presumably further reduced capacity to produce myelin).
The team then re-introduced the socially isolated mice back into a social group. After four weeks, their social withdrawal symptoms had gone, and the tissue analysis showed the gene expression changes had reversed.
The researchers conclude their findings suggest myelin formation “acts as a form of adult plasticity”, and that formation of new oligodendrocytes is affected by environmental changes.
“Our study demonstrates that oligodendrocytes generate new myelin as a way to respond to environmental stimuli, and that myelin production is significantly reduced in social isolation,” says Casaccia.
The study supports other emerging evidence that abnormal myelin contributes to a range of psychiatric disorders, including anxiety, autism, schizophrenia and depression, as Casaccia explains:
“Abnormalities occur in people with psychiatric conditions characterized by social withdrawal. Other disorders characterized by myelin loss, such as MS, often are associated with depression.”
“Our research emphasizes the importance of maintaining a socially stimulating environment in these instances,” she adds.
Casaccia’s lab at Mount Sinai is now looking more closely at oligodendrocyte formation to see if there might be some suitable targets for drug development. They are testing candidate compounds in rodent and human brain cells, for their effect on new myelin production.
Funds from the National Multiple Sclerosis Society, and the National Institute of Neurological Disorders and Stroke, a division of the National Institutes of Health, helped finance the study.
Written by Catharine Paddock PhD