The body’s immune system reacts to an injury or infection by causing inflammation, which initiates the healing process. However, there are many less beneficial situations in which inflammation can arise, such as psychological stress or a poor diet high in fats, sweets, and processed foods. Pregnancy-related inflammation raises the baby’s risk of issues, especially for neurodevelopmental diseases like autism, ADHD, and learning difficulties. A new grant from the Burroughs Wellcome Fund has been awarded to a researcher at the University of Oklahoma to investigate how the inflammation during pregnancy impacts child neurodevelopment and whether there is a way to make the fetus more resistant to inflammation.
“The underlying theme for this research is inflammation during pregnancy. It’s not inflammation in response to an active infection like a virus might cause, but the inflammation is similar regardless of the type of stressor. Our work is focused on finding a mechanism that can promote resilience across a number of different stressors rather than a specific one.”- Lindsay Hayes, PhD, Assistant Professor, Cell Biology, OU College of Medicine, OU Health Sciences, The University of Oklahoma
How the study is carried out
Hayes is trying to learn more about the activity of a particular kind of immune cell, called microglia, which are the main immune cells in the brain, in order to better understand resilience. The microglia enter the developing embryo’s brain early in pregnancy and stay there until the brain is fully formed. Microglia are suited to sense inflammatory responses brought on by stressors experienced by mothers because it is their function to react to changes in their surroundings.
The microglia are somehow “reprogrammed” to be less effective at their jobs when they experience increased inflammation. This thus creates the conditions for difficulties like early birth, growth restriction, and stillbirth, as well as potential problems with the brain development of the embryo.
The microglia basically assume that they will witness a lot of inflammation in the future given the current state of inflammation. They thereby lower their threshold for reacting to upcoming stimuli, preparing themselves for a life of extreme stress. In this manner, they prevent an overreaction and an excess of immunological signals, according to Hayes.
The body’s mechanism for generating and utilizing energy, known as metabolism, is one method immune cells attempt to adapt. But because of the way inflammation has affected them, the microglia might not be metabolically fit, meaning they lack the energy to generate a healthy immune response. As a result, they might be less effective in their regular role of guarding the growing brain. “So we want to make this connection between metabolic fitness and immune fitness,” Hayes stated.
Two distinct study frameworks
Hayes is comparing prenatal inflammation in two distinct mice study models in order to test her theories. Maternal immunological Activation is one of them. The mouse is given a chemical that causes inflammation and an immunological response that lasts for a few days, just like if a pregnant mother had an infection. The mice in the other model, dubbed the Maternal Western-Style Diet, are fed a diet heavy in fat, typical of the Western world. Chronic, low-level inflammation is the result of this.
“We’re hoping we can tease apart what makes some mice susceptible to stressors while others are more resilient,” she said. “The connection between immune and metabolic function and the microglia is a new area of research that I think will continue to grow. It’s an exciting opportunity to better understand how the immune system can impact the nervous system.”
Hayes intends to provide an antioxidant called pyrroloquinoline quinone, or PQQ, which is present in fruits and vegetables and has anti-inflammatory qualities, to the Maternal Immune Activation mice in addition to comparing the two study models. According to current studies, obese mothers who take PQQ can prevent adult fatty liver disease in their offspring. In a similar vein, Hayes hopes PQQ can reduce inflammation brought on by a psychological stressor.
“We hope we can develop an intervention that can help no matter what leads to the increase in inflammation,” she stated. “This is a challenging area of research, but that’s also what makes it most exciting.”
Source Link: University of Oklahoma
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