National Primate Research Centers Prioritize Openness for Scientific Progress

At the forefront of biomedical and behavioral research are the seven National Primate Research Centers (NPRCs). They form a vital network dedicated to conducting and enabling groundbreaking research to improve human and animal health. Studies at the centers include development & aging, genetics & genomics, infectious disease, neuroscience & brain disorders, and reproduction & endocrinology. The NPRCs have been instrumental in driving discoveries crucial for overcoming health challenges and in helping the public understand the significance of research that involves animals.   

A Comprehensive Approach  

A priority of the NPRCs is to share information via local, regional and national outreach. Through a multifaceted approach, the NPRCs foster education and dialogue, ensuring openness about their research and the expert care of animals involved in NPRC research studies.   

From participating in local events to leveraging digital platforms, the NPRCs employ diverse strategies to make connections. NPRC.org provides the latest information for the public, and NPRCresearch.org, which is undergoing updates, ensures the scientific community has comprehensive information about the resources the NPRCs offer NIH-funded researchers. Through timely and engaging content, the NPRCs strive to explain the highly regulated research process and showcase their contributions to scientific progress.   

A Legacy of Excellence  

With a history spanning more than six decades, the NPRCs stand as pillars of scientific expertise and exemplars of public outreach. The U.S. Animal Research Openness initiative (USARO) recently featured information about the NPRCs’ outreach programs on the USARO website. This article provides encouragement for other research centers to follow the NPRC lead.   

A Future Filled with Accurate Information  

As the NPRCs continue to make scientific discoveries, their dedication to openness will continue to expand. The NPRCs believe openness helps empower individuals to make informed decisions, is critical to instilling confidence in scientific research and care of research animals, inspires future generations of scientists and ensures the public has accurate information about how research with animals is improving lives.  

Every day, the seven National Primate Research Centers (NPRCs) conduct and enable collaborative research studies to improve human and animal health. For more than five years now, we’ve been sharing our latest news and scientific advancements with you via NPRC.org and @NPRCnews (X), and there’s more coming your way. 

To ensure the NPRCs provide the topics of most interest to our readers and followers, we looked back at your favorite stories to help us move forward. Your top interests span behavior and psychology, infectious disease and neuroscience and brain disorders research. We will continue to share news that represents what you have most enjoyed, and we will also bring you information that reflects the breadth and depth of research across the NPRC network.   

We appreciate our readers and followers, and encourage you to take another look at your favorite blogs about NPRC research, to share the information with your family, friends and colleagues, and to continue connecting with us via NPRC.org, @NPRCnews and, now, on the new NPRC LinkedIn account. Via these resources, you’ll always be able to access the latest news on NPRC research that is helping people across generations and around the world live longer, healthier lives.   

Behavior and Psychology 

1. The Effects of Wildfire Smoke Exposure in Early Pregnancy 

A study by California NPRC and UC Davis researchers investigated the effects of wildfire smoke exposure on infant monkeys during early pregnancy. The study found that exposure led to increased inflammation, reduced stress response, memory deficits and a more passive temperament in the monkeys. The findings suggest environmental changes during pregnancy can have lasting effects on offspring.  

Infectious Disease 

2. A Deadly Relationship: Stopping the Progression of Tuberculosis in HIV Patients   

Researchers at the Southwest National Primate Research Center have discovered chronic immune activation in the lungs plays a crucial role in the progression of tuberculosis (TB) and HIV co-infection. This dysfunction hampers the body’s ability to fight off infections. The study suggests the need to develop treatments targeting chronic immune activation alongside antiretroviral therapy (ART). TB and HIV are global pandemics that reinforce each other, affecting a significant portion of the world’s population. The findings offer hope for improved treatment strategies in the next decade. 

3. New Possible Correlation Between Lyme Disease and Lewy Body Dementia  

At Tulane National Primate Research Center, researchers discovered intact spirochetes of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the central nervous system of a 69-year-old woman who received multiple rounds of antibiotic treatment. The presence of this bacterium coupled with her persistent neurological decline raises the possibility of a correlation between Lyme disease and Lewy body dementia. This finding highlights the bacterium’s persistence despite targeted therapy and emphasizes the need for further research to comprehend its role in severe neurological conditions. 

4. Are DNA Vaccinations a Perennial Answer to the Flu?  

Researchers at the Washington National Primate Research Center are developing a universal flu vaccine that could protect against all strains of the influenza virus. Using a DNA vaccine administered through the skin, the team has achieved promising results in macaques, providing 100% protection against a previous flu virus. This approach could eliminate the need for annual flu shots and be quickly deployed during pandemics. The researchers believe this technology could also be effective against other viruses and outbreaks. 

Neuroscience & Brain Disorders 

5. Past Social Experiences May Affect Brain’s Response to Oxytocin

A study at the Emory (formerly Yerkes) National Primate Research Center and Emory University showed the response of neurons to oxytocin, a chemical involved in social bonding, can vary based on an individual’s past experiences. Using female prairie voles, the researchers examined the nucleus accumbens, a brain region related to pair bonding. They found that oxytocin reduced neuron firing before bonding and increased it afterward, when triggered. The study also revealed a connection between oxytocin signals and endocannabinoids, affecting defensive interactions. These findings provide insights into how prior experiences influence oxytocin’s impact on brain circuits. 

6. NPRC Study May Have Found Link That Causes Anxiety and Depression  

Researchers at the Wisconsin National Primate Research Center and the University of Wisconsin-Madison have discovered brain pathways in juvenile monkeys that could contribute to anxiety and depression later in life. By studying the connections between specific brain regions, they found a correlation between synchronization and anxious temperament. These findings may lead to better treatment approaches and help identify gene alterations associated with anxiety. 

7. The Drinking Gene: Could Alcoholism Be Inherited?  

Research conducted at Oregon National Primate Research Center has identified a gene, GPR39, as a potential target for developing medication to prevent and treat alcoholism. By modifying protein levels encoded by this gene in mice, the researchers observed a significant reduction in alcohol consumption. They also found a link between alcohol and the activity of this gene. The study draws attention to the importance of cross-species approaches to identify drugs for treating alcohol use disorder. Further investigations are under way to determine if the same mechanism applies to humans. These findings offer potential insights for developing drugs to address chronic alcoholism and mood disorders. 

The battle against COVID-19 has been relentless, and scientists at Emory University and researchers from collaborative institutions worldwide are leaving no stone unturned in their quest for innovative treatment options. In an exciting breakthrough, researchers at Emory’s NPRC and their colleagues have delved into the intricate world of type 1 Interferon (IFN-I) signaling, a key player in our body’s defense against infections. Their groundbreaking study, conducted with nonhuman primates, offers a fresh perspective on combating SARS-CoV-2, and paves the way for potential new treatments for COVID-19. 

The Defender: Type 1 Interferon 

Senior author, Mirko Paiardini, PhD, and his team focused on understanding the role of IFN-I in SARS-CoV-2 infections. IFN-I is like the first responder in our body’s defense mechanism, acting swiftly to thwart viral replication when an infection is detected. This study, a first in nonhuman primates, sheds light on how tweaking IFN-I signaling can impact viral replication and the progression of COVID-19. 

The Balancing Act: IFN-I’s Double-Edged Sword 

The findings of the Emory University study illuminate a delicate balance in the fight against COVID-19. While early IFN-I responses are crucial for containing SARS-CoV-2, an excess of IFN-I signaling can lead to hyperinflammation in the body, contributing to severe disease. This discovery underscores the importance of timely intervention to prevent excessive inflammation, a primary driver of severe COVID-19 cases. 

Dr. Paiardini, Division Chief of Microbiology and Immunology, Professor of Pathology and Laboratory Medicine, and Co-Director at the Emory Center for AIDS Research, emphasizes the significance of this balance and the need to fine-tune the body’s immune response to combat the virus effectively. 

The Experiment: IFNmod to the Rescue 

Researchers used a modified version of interferon, aptly named IFNmod, in rhesus macaques before and during acute SARS-CoV-2 infection to modulate IFN-I signaling. The results were nothing short of remarkable. IFNmod treatment weakened antiviral and inflammatory gene expression, leading to lower levels of inflammatory cytokines in the lower airways. This reduction in inflammation correlated with reduced lung pathology.  

“We were also surprised to find IFNmod treatment had a profound effect on SARS-CoV-2 viral loads, with a 3,000-fold reduction in viral loads in the lower airways of treated animals,” says co-first author Elise Viox.  

Emory University’s groundbreaking research into modulating type 1 Interferon signaling offers hope in our battle against COVID-19. By striking the delicate balance between immune response and inflammation, we’re closer to effective treatments for this tenacious virus.  

The Influence of Social Status on Early Social Development: Insights from Maturing Visual Pathways

 Forming infant-caregiver bonds is critical to social and neural development during infancy. However, the underlying brain pathways supporting infant attention to others’ eyes have remained largely unknown. Recent groundbreaking research conducted at the Emory National Primate Research Center (EPC) and the Marcus Autism Center sheds light on the development of eye contact behaviors in infant rhesus macaques and their influence on brain growth. This research not only has the potential to reveal early neurobehavioral markers of social disability but also provides insights into the impact of social status on these developmental processes.

“For both humans and macaques, learning to engage with the eyes of others during infancy is a critical social skill in typical neurodevelopment,” says senior author Mar Sanchez, Ph.D. Exploring the brain regions and environmental factors that contribute to this behavior can enhance our understanding of its emergence and role in primates’ social development.

Studying Infant Macaques

The research team conducted a study involving male infant macaques, measuring their eye contact behaviors through eye-tracking tools while showing them videos of other macaques. Resting-state functional MRI (rs-fMRI) scans were also taken to analyze connectivity within the occipital and temporal cortices, which are involved in visual perception and social processing.

The researchers collected data from two weeks to six months old at regular intervals. This unique longitudinal dataset allowed them to observe changes in the connectivity patterns between the occipital and temporal cortices over time. They discovered that the most significant changes occurred during the first three months of life, which is analogous to humans’ first year of life.

Importance of Brain Connectivity and Influence of Social Status

Infants with stronger connections between the brain areas responsible for visual processing (primary visual areas) showed a greater tendency to make eye contact with other monkeys earlier than infants with weaker connections. The study also revealed that social status impacted the relationship between brain maturation and eye contact. Low-ranking infants displayed a stronger association between the development of visual pathways and eye contact compared to their high-ranking counterparts. This suggests that low-ranking infants may have adapted brains that facilitate early identification of faces and expressions, enabling them to navigate social interactions more effectively.

Implications for Human Development

Aiden Ford, the first author and a Ph.D. candidate in Neuroscience at Emory, highlights the influence of social status on the development of the social brain, even in the earliest postnatal months. This research provides unique insights into brain and behavior development dynamics at both the group and individual levels. It also raises the possibility that early exposure to adversity may accelerate biological, brain, and social development.

The research group plans to conduct further studies mapping the development of social behaviors and social brain regions in infant macaques. The amygdala, a critical part of emotional processing, will be a particular focus. Additionally, the effects of infant social status will continue to be investigated, providing a deeper understanding of how social factors shape neural development.

Oxytocin is a hormone that plays a critical role in social bonding and attachment. In recent years, researchers have been studying the effects of intranasal oxytocin, a non-invasive treatment that reduces social impairment in several neurological and behavioral disorders, such as autism.  

However, the long-term effects and efficacy of the treatment are currently under examination. Studies conducted by Dr. Karen Bales’ lab at the California National Primate Research Center reveal that chronic intranasal oxytocin produces sex-specific biological and behavioral responses in titi monkeys, a monogamous nonhuman primate.  

The researchers found that all OT-treated monkeys engaged more in social interactions but differed in their social behavior by sex. The males exhibited more social interest in unfamiliar animals, while females directed their interest toward their parents.  

The monkeys were divided into two groups: one received a daily dose of intranasal OT, while the other received saline for six months. The treatment group exhibited more prosocial behavior in their home enclosure immediately following their dose than the control group. 

Researchers also examined neural effects and social behavior during adolescence and into adulthood one-year after treatment ended. As adults, males from the treatment group maintained some prosocial effects. They also scored higher on several measures of affiliative behavior than the control group. Females, however, experienced a slight delay in forming a bond with their new mate. 

The researchers observed that chronic treatments during adolescence altered their behavior long-term, and these behavioral changes were different for males and females. These findings emphasize the complexity of the treatment and lay an essential foundation for more research on its use in humans. 

A collaborator on the project, Dr. Suma Jacob from the University of Minnesota Medical School, explained that “there is more research to be done on oxytocin, how it works, its effects, and feedback systems.”

Marina Emborg, medical physics professor and director of the University of Wisconsin–Madison’s Preclinical Parkinson’s Research Program, focuses on understanding and developing treatments for neurological disorders in a highly collaborative, interdisciplinary fashion. 

In her article, “Reframing the perception of outliers and negative data in translational research,” published last month in Brain Research Bulletin, Emborg describes how publishing negative or unexpected data from a research project helps scientific research advance. 

Scientific results are termed ‘positive’ when supporting the driving hypothesis and ‘negative’ when countering it. Both can be equally informative. But it is noteworthy that ‘negative’ data differs from ‘useless’ data. 

• Useless data is defined as the results obtained by a biased or poorly performed experiment. 
• Negative data are unexpected results that prove or disprove a hypothesis in a way not previously known. 

“Overall, the paper aims to reframe the perception of working with, reporting and reviewing unexpected data as an opportunity to provide rationale for innovative ideas, prevent the misuse of limited resources and, ultimately, strengthen the reputation of a scientist,” writes Emborg in the paper’s abstract. 

While scientists may be initially disappointed by negative data, analyzing it is helpful for the scientific community, including individual scientists, explains Emborg, whose lab is based at the Wisconsin National Primate Research Center. 

Through a new study with marmosets, scientists are learning more about how neuroestrogens may be integral to supporting libido and maintaining female sexual health. 

“The lack of effective treatment options for women with Female Sexual Interest Arousal Disorder (FSIAD) and obesity is likely related to the lack of understanding regarding the biology of female sexuality, as well as the regulation of body weight and metabolism,” reports first author Marissa Kraynak, Ph.D. Kraynak was a research fellow in the Endocrinology and Reproductive Physiology Program at the University of Wisconsin–Madison when the study was underway, training under David Abbott, Ph.D., and Jon Levine, Ph.D., at the Wisconsin National Primate Research Center. She is now the Director of Health Policy Research at Insure the Uninsured Project in Sacramento. 

Doctors often give women synthetic estradiol to compensate when women need ovariectomies due to cysts, cancer, or other problems. But ovarian estradiol, found in the skin, adipose tissue, brain, and ovaries, can cause harmful side effects, including cardiovascular disease and cancer. 

Kraynak reported bioactive estradiol derived from the brain, as opposed to the ovaries, plays a pivotal role in maintaining sexual receptivity in female nonhuman primates. During the study at the University of Wisconsin–Madison center, the ovarian estradiol-depleted female monkeys remained receptive toward at least 35 percent of male mounting behaviors.  

Only by removing both ovarian and extra-ovarian estradiol, including hypothalamic sources, were female marmosets consistently sexually unreceptive to male sexual advances. This study provides hope for better treatment options for women with Female Sexual Interest Arousal Disorder (FSIAD) and obesity. 

Ceramides are fats or lipids found in skin cells and make up approximately 35% of your outer skin layer. They are widely known for retaining skin moisture and preventing germs from entering the body. But now they could also be used as early clinical detectors of the onset of metabolic syndrome – a cluster of conditions that increase the risk of heart disease, stroke, and type 2 diabetes.

Researchers at the Wisconsin National Primate Research Center used rhesus monkeys during a two-year ceramides study. Rhesus monkeys are similar in metabolic function to humans and, like people, can get obesity, diabetes, heart disease, high blood sugar and high blood pressure. The researchers fed 16 genetically diverse, healthy yet overweight adult monkeys the same diet and kept them in a controlled environment. Half developed metabolic syndrome and showed significant composition differences of circulating ceramides when compared to monkeys who did not develop the syndrome.

“Seeing these differences earlier on, when animals were clinically indistinguishable from one another, provides new insight on metabolic impairment and how we might distinguish among individuals to identify those at elevated risk for disease,” Anderson said.

As metabolic syndrome becomes increasingly more common among humans, currently affecting about a third of U.S. adults, the necessity of early preventive strategies is critical.

While current HIV treatment reduces viral load, or the amount of HIV in the blood, there is no cure for the disease. Antiretroviral therapy (ART) involves either taking a shot or a daily pill. Then a test can’t often detect HIV because the viral load becomes so low. Unfortunately, skipping a treatment, even now and then, gives the remaining virus a chance to multiply rapidly, weaken the immune system and cause illness. 

A truly effective treatment for chronic HIV infection would eliminate these residual infected cells, known as the HIV reservoir. A drug called N-803, developed by ImmunityBio, Inc., has the potential to be such a therapeutic. N-803 is now in clinical trials for treating non-muscle invasive bladder cancer that does not respond to standard therapy. The drug received Fast Track and Breakthrough Therapy designations in 2017 and 2019, respectively, from the U.S. Food and Drug Administration (FDA) for this cancer based on its demonstrated activity as a compound that stimulates the immune system. 

Shelby O’Connor, a professor of pathology and laboratory medicine at the University of Wisconsin–Madison and a scientist at the Wisconsin National Primate Research Center, recognized that N-803 might also have the potential to treat HIV. She and her research team evaluated this drug’s effectiveness in the context of various immune states and concurrent therapies in simian immunodeficiency virus (SIV) models, using both rhesus and cynomolgus monkeys. 

The researchers discovered overall that primates with low viral copies before N-803 treatment improved their ability to kill SIV during treatment. Primates with higher viral load before treatment showed chronic activation of T-cells, resulting in immune “exhaustion” and leaving these immune cells that target SIV unable to fight viral infection even with the treatment. 

This NIH-funded research suggests the drug is most effective in hosts with a natural pre-existing immunological ability to control SIV replication. This aligns with N-803’s known ability to increase the proliferation of both natural killer cells and T cells in hosts with higher-functioning immune systems. 

The O’Connor lab plans to continue investigating how N-803 may react differently in individuals that control HIV and SIV compared to settings where the virus is not controlled.

HIV, human immunodeficiency virus, destroys CD4 cells, also known as helper T cells, in the immune system. Without these cells, bodies have a hard time fighting off various diseases. While there is currently no cure for HIV, people now live long and fulfilling lives with it when treated medically.

Long-term medical treatment isn’t ideal, however, making the fight far from over. Researchers are constantly looking for ways to develop new treatments. One reason HIV is hard to eliminate is its ability to escape drug treatment by hiding in the body, including in the lymph nodes and spleen.

Infected cells hole up in an area of the lymph tissue called the B cell follicles. Immune cells, including T cells and natural killer (NK) cells, whose job is to kill virally infected cells, are generally unable to reach the B cell follicles, making them a safe space for the virus.

Using findings from a previous study published in the Proceedings of the National Academy of Sciences in 2017 focused on B cells, a research team at Emory National Primate Research Center (EPC) studied rhesus macaques with chronic SIV infection.  

“Infiltration of these highly cytotoxic NK cells in the B cell follicles has never been shown before during chronic HIV/SIV,” says senior author Vijayakumar Velu, Ph.D., an assistant professor in the Division of Microbiology and Immunology at the EPC. “This study has implications for developing new cure strategies for HIV, as these cells traffic to B cell follicles during controlled infection,” says co-author Rama Amara, Ph.D.

While more research is needed before introducing new treatments to humans, it’s a huge step in ultimately finding a cure for those living with HIV.