According to a recent survey by the American Psychological Association, three out of every four Americans reports experiencing a symptom of stress in the past thirty days. We are constantly faced with all kinds of stressors—personal, financial, career, news, and so on—with increasing frequency particularly as the role of mobile communications continues to grow in daily prevalence.
A scientific understanding of how this is detrimental in the long run has been growing, with studies revealing that exposure to stressors ranging from violence all the way to social conflict significantly increase the risk for major psychiatric conditions like depression and post-traumatic stress disorder (PTSD); but researchers are still evaluating how the long-term ramifications of individual exposure to stress develop.
Researchers at the Advanced Science Research Center (ASRC), part of The Graduate Center at CUNY, recently made huge strides in elucidating the effects of stress while also shedding light on a type of cell that has sometimes baffled scientists. These CUNY researchers identified that the glial cells that form myelin sheaths in the central nervous system, known as oligodendrocytes, are key deciders in whether or not stress will negatively impact us, and may be affected by epigenetics.
These researchers took a uniform group of mice and exposed them to the same “social-defeat stressor” in the form of another aggressive mouse. The first mouse would either remain socially engaged—and therefore were classified as “resilient”—or they would avoid the aggressor, making them members of the “susceptible” group of animals.
The brain tissue of the animals was then examined using staining methods and electron microscopy, with samples taken from the medial prefrontal cortex due to its known vital role in both emotional as well as cognitive processing; tissue samples were compared to see if there were any noticeable differences between the susceptible versus resilient mice. Of course, there was also a control group of mice to establish a baseline reference for comparison and so to make sure that all of the observations were valid—not just a misinterpreted artifact of the experiment performed.
Indeed, tissue taken from the susceptible mice showed fewer oligodendrocytes, and the myelin coverage in this brain region was noticeably and consistently irregular, shorter, and thinner compared to that of the resilient mice. The team found reduced levels of histone methylation in the irregular cells, indicating the epigenetic modification may be responsible for the impaired oligodendrocyte differentiation.
Histone methylation is the addition of methyl groups to a lysine by a histone methyltransferase. It is a versatile epigenetic mechanism, as it results in gene activation or repression, depending on its specific target.
But while the reduction in quality and quantity of oligodendrocytes here was visible, it did not seem permanent; this suggests that some other regulation mechanism beyond the genetic sequence—which centrally governs development—is at play.
The idea that stress can affect the epigenetic modification of oligodendrocyte progenitors—controlling their proliferation—could account for the switch-like mechanism that stress seems to flip in an individual’s myelination patterns; after all, when new myelin forms, its characteristics return to normal, suggesting that whatever changes result from this stress are not permanent damage to the genetic code.
As Patrizia Casaccia, founding director of the Neuroscience Initiative at the ASRC notes, “[This] research has highlighted the importance of stressful social events in changing the epigenetic code of oligodendrocyte progenitors, which may account for the increased susceptibility to developing chronic psychiatric disorders in some individuals.” But pointing to a cause alone is not enough; the greatest long-term research value comes from shedding light on potential mechanisms that use this knowledge to treat disease. “[The] data suggest that oligodendrocyte progenitor differentiation can be affected by emotional and psychological events, and this provides a new concept for preventing and treating depression.”
The complexity of psychiatric disorders underscores the importance of discovering any sort of enlightenment regarding its causes. Understanding the changes that stress effects on the body in turn allows researchers to start mapping potential clinical interventions, with the ultimate goal of reducing its negative effects and preventing psychiatric disorders. Most current therapies focus on neuronal health, but this research points to the potential for intervening on glial cells, at least in the event of stress-related mental illness.
Reference: Advanced Science Research Ctr.. “Researchers Identify Glial Cells as Critical Players in the Brain’s Response to Social Stress.” The Graduate Center, CUNY. August 13, 2019
Source: Valentina Bonnefil, et al. Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice. Research Communication eLife;8:e40855 2019.