It appears that being isolated during childhood prevents the cells in the brain’s white matter from developing and producing the correct amount of myelin, the fatty “insulation” on nerve fibers that helps send out long-distance messages within the brain.
Furthermore, the researchers pinpointed a molecular pathway involved in these abnormalities, and the timing of social deprivation is an important factor in causing its dysfunction.
Studies of children who grew up in institutions with severe neglect have shown changes in white matter in the prefrontal cortex, but the mechanism for the changes was unknown.
For the new study, researchers at the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, modeled social deprivation in mice by isolating them for two weeks.
During a “critical period,” starting three weeks after birth, isolation kept cells (called oligodendrocytes) from maturing in the prefrontal cortex—a region important for cognitive function and social behavior. As a result, nerve fibers had thinner coatings of myelin, which is produced by oligodendrocytes, and the mice showed difficulties with social interaction and working memory.
The new study adds to a growing body of research that glial cells, including oligodendrocytes, do more than just support neurons, but rather participate actively in setting up the brain’s circuitry as they receive input from the environment.
“In general, the thinking has been that experience shapes the brain by influencing neurons,” said study leader Gabriel Corfas, Ph.D., who holds an appointment in the Departments of Neurology and Otolaryngology at Boston Children’s Hospital and Harvard Medical School.
“We are showing that glial cells are also influenced by experience, and that this is an essential step in establishing normal, mature neuronal circuits. Our findings provide a cellular and molecular context to understand the consequences of social isolation.”
Myelin is vital for healthy communication between different areas of the brain, so the weaker myelination could explain the social and cognitive deficits in the mice. Corfas has previously shown that abnormal myelination alters dopaminergic signaling in the brain, which could add another explanation for the findings.
The new study also shows that the effects of social isolation are time-sensitive. If mice were isolated during a specific period in their development, they failed to recover functioning even when they were put back in a social environment. On the other hand, if mice were isolated after this so-called critical period, they remained normal.
Finally, Corfas and colleagues identified a molecular signaling pathway through which social isolation leads to abnormal myelination.
“These observations indicate that the mechanisms we found are necessary for the brain to ‘benefit’ from early social experience,” said Corfas.
The Corfas lab is now investigating drugs that might stimulate myelin growth.
“Having both too much and too little myelination is bad,” Corfas says. “This is a pathway that requires very careful regulation.”
Manabu Makinodan, M.D., Ph.D., a postdoctoral fellow in Corfas’ lab, was first author of the paper, published in the journal Science.
Source: Boston Children’s Hospital