Stereo Investigator Helps Harvard Scientists Study Social Isolation’s Effects on the Brain

Some children raised in orphanages grow up to develop social disorders, and there’s not all that much modern medicine can do about it. But scientists at Harvard Medical School are working on gaining a better understanding of how early isolation affects a developing brain. Their research gives new insight into the mechanisms at play, and indicates that timing and healthy myelination are crucial.

“Social isolation from P21 to P35 alters [medial Prefrontal Cortex] oligodendrocyte morphology, myelination, and mPFC-mediated behaviors,” the authors say in their paper, published in Science. “These effects persist even when isolated mice are re-exposed to social interactions, which suggests a link between the quality of mPFC myelination established during the juvenile period and adult behaviors.”

Led by Dr. Manabu Makinodan, the research team studied three groups of male mice. At 21-days-old, the mice were caged according to different scenarios: isolated environment (alone),  regular environment (with three other mice), or enriched environment (with seven other mice and a selection of toys). Four weeks later, testing showed deficits in social behavior and memory in the isolated mice.

To determine what went wrong in the brains of the isolated mice, the researchers examined the oligodendrocyte neurons in the prefrontal cortex, a brain region integral to social behavior. They determined that the density of oligodendrocytes was the same in all three groups, by using Stereo Investigator with the optical disector to perform a stereological count. Although density was consistent, the morphology of oligodendrocytes in the brains of the isolated mice was remarkably different. These mice displayed a simpler morphology that included “shorter processes, less branching, and fewer internodes.” Their myelin sheaths were thinner, resulting in decreased signaling between neurons and altered information processing.

Further trials showed that mice isolated later in life, after 35 days of age, showed the same morphology as normally reared mice, indicating that the critical period for development is before 35 days. They also noticed that mice isolated from 21 days, and which were later returned to normal environments, still showed abnormal morphology, implying that the detrimental effects of isolation could not be reversed.

“Our findings indicate that the effects of childhood isolation and neglect on adult mental health might be caused, at least in part, by alterations in oligodendrocytes and myelin development. Furthermore, we provide a cellular and/or molecular context and genetic models in which to begin to understand the effects of juvenile social experience on brain development in general and myelin maturation in particular. Our results also may be relevant to neuropsychiatric disorders such as schizophrenia and mood disorders” (Makinodan, et al, 2012).

Access the paper “A Critical Period for Social Experience–Dependent Oligodendrocyte Maturation and Myelination” at ScienceMag.org.

Manabu Makinodan, Kenneth M. Rosen, Susumu Ito, and Gabriel Corfas. “A Critical Period for Social Experience–Dependent Oligodendrocyte Maturation and Myelination.” Science, 2012; 337 (6100): 1357-1360 DOI: 10.1126/science.1220845

Image of Oligodendrocyte courtesy of Harvard Medical School.

Multiple Sclerosis and Schizophrenia Research May Benefit From New Findings

Myelin, which insulates axons in the central nervous system is produced by oligodendrocytes. But not all oligodendrocytes are equal.

Led by Dr. Jonathan Vinet of the Université Laval in Quebec, scientists have identified three different types of oligodendrocytes in the mouse hippocampus: “ramified,” “stellar,” and “smooth.”

Each type displayed varying morphological characteristics, mainly in shape, volume, and branching behavior, which led the researchers to believe that the three types represent different stages of maturation.

As described in the paper, “Subclasses of oligodendrocytes populate the mouse hippocampus,” published in the European Journal of Neuroscience, the “smooth,” or most simple type possibly morphs into the “stellar,” which eventually develops into the most complex of the three, the “ramified” oligodendrocyte.

The identification of these morphologically distinct oligodendrocyte populations in the hippocampus may help researchers determine which specific types of oligodendrocytes are affected in diseases such as schizophrenia and multiple sclerosis.

Using a Neurolucida system with an Olympus AX-50 microscope, the scientists formed 3D reconstructions of the hippocampal oligodendrocytes integral to their study. They then analyzed their tracings with Neurolucida Explorer.

“Without Neurolucida we couldn’t have carried out this study,” said Dr. Attila Sik, “it was an essential component. Nice piece of equipment, for sure.”

Read the free abstract, or access the full article (by subscription), at the European Journal of Neuroscience.

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