January 2024
Jessica Raper fell in love with primate research as an undergrad and hasn’t looked back. Dr. Raper says monkeys are a good model for understanding human health because they have similar immune systems, brain structures and developmental timing. Together with Dr. Ann Chahroudi and Dr. Mehul Suthar, she is looking at the impact of postnatal Zika virus infection. There’s a lot of research on fetal Zika virus exposure and the impact on a developing infant, but little is known about postnatal infection. Dr. Raper uses monkeys as a model to understand how Zika getting into the brain may impact the development of the brain, behavior, and cognitive function.
How can you measure the effect of Zika infection on an infant monkey? Dr. Raper says that many of the tests she uses are adapted from tests used in humans, making them directly translational. One test involves looking at the stress response similar to the stranger approach task. Just like with human children, we observe how the monkey responds to either direct or averted gaze from a strange person entering the room. This approach helps to look at anxiety behavior of the monkeys. Other tests use eye tracking and present videos on a screen to see where animals are looking in order to see how they process social stimuli or remember objects.
Another part of the research project involves looking at vulnerability to Zika virus depending on the age of the monkey. A one-month-old monkey corresponds to a four-month-old human infant, while a seven-month-old monkey would be similar to a two-year-old toddler. Dr. Raper wants to understand how Zika infection may have a greater effect on the brain depending on the developmental stage. Using MRIs, she can see how the brain is changing over time and how those changes may explain behavioral alterations to pediatric Zika infection.
The most prominent finding is that Zika infection in infant monkeys resulted in an increased lateral ventricle size and decreased hippocampus volumes. Dr. Raper and colleagues recently conducted a pilot study funded by the Children’s Center for Neuroscience Research (CCNR) to examine a post Zika exposure antiviral treatment and found it helped mitigate some negative impacts, but it was an intermediate affect. The treated monkeys were better on social behavior and their brain development was somewhat better, but not up to par with the control group.
Dr. Raper’s current R01 is focusing on the impact of postnatal Zika and understanding its mechanism. Is it targeting dividing cells like newly developing neurons? Is it a neuroinflammatory response that is impacting brain development long term? The top goal for this research is to understand mechanisms and see whether there’s a critical window of vulnerability.
There was a lot of focus on fetal exposure when the 2015 Zika epidemic happened in South America. Being a developmental neuroscientist, Dr. Raper was curious how Zika might impact infants or toddlers, because their brains are rapidly growing. She recalled that her twin boys were one-years-old when Zika started, so they partially inspired her to study early postnatal infection.
Another research project Dr. Raper is working on is understanding the impact of early exposure to anesthesia. Does it have a neurotoxic impact on the early developing brain? Preclinical animal studies show that it can. Some clinical trials show there’s an increased risk in learning disabilities if kids have three or more anesthesia exposures before four-years-old. Dr. Raper found that repeated anesthesia lead to increased anxious phenotype in her monkeys. Now she is trying to learn how to protect the developing brain during anesthesia exposure. There are several hypotheses on what the mechanism is; one including that anesthesia can cause neuroinflammation and mitochondria damage, as shown in animals. Dr. Raper’s research looks at whether pramipexole administration can protect the mitochondria and mitigate the effects of early anesthesia.