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. 

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.

Human immunodeficiency virus (HIV) attacks the body’s immune system, resulting in rashes, fevers, fatigue, swollen lymph nodes, and other symptoms. It affects over 37 million people globally. When left untreated, HIV infections can progress to acquired immunodeficiency syndrome (AIDS), leading to a damaged immune system, severe opportunistic infections, and death.

Most replicating HIV – and its monkey version, simian immunodeficiency virus (SIV) – is found in follicles of the lymphoid tissues. However, most cytotoxic T-lymphocytes, the cells clearing HIV from the body, cannot reach the follicles. This explains the need for lifelong use of antiretroviral therapy’s current standard treatment. However, only 57% of those living with HIV are undergoing antiretroviral therapy, which leaves the rest able to infect others with the virus. Therefore, there is an urgent need for new treatment options, especially for those who do not have lifelong access to healthcare.

A group of AIDS researchers working with immunology and animal care experts on rhesus monkeys at the Wisconsin National Primate Center investigated the possibility of a new therapy targeting virus-specific T-cells to the follicles. They did so by engineering therapeutic T-cells to enter and concentrate in the lymphoid follicles to reduce viral replication. Led by Pamela Skinner, professor of veterinary and biomedical sciences at the University of Minnesota, the team used T-cells to express a chimeric antigen receptor (CAR) targeting the SIV virus. They added a follicular homing receptor called CXCR5 so the CAR/CXCR5 T-lymphocytes could kill the infected cells in the lymphoid follicles. The homing receptor allowed the T-cells to migrate into the follicles, which previously limited the effectiveness of the body’s response to infection.

In six SIV-infected rhesus monkeys, the CAR/CXCR5 T-cells were able to migrate to the follicles within two days and directly interact with the virally infected cells. Fluorescent imaging allowed the researchers to discover these T-cells could replicate and increase within the follicles. Even though levels of the specialized T-cells declined within four weeks after administration, the treated primates were able to maintain lower concentrations of SIV in their blood and follicles than those not given the CAR/CXCR5 T-cell immunotherapy. The researchers and veterinarians also looked at possible side effects of this treatment and found none of the primates had a poor reaction to T-cell administration.

The study, published in Public Library of Science Pathogens, provided preliminary evidence for effective and safe treatment of engineered T-cells for HIV infection. Data from these researchers set the stage for future preclinical studies involving larger populations of non-human primates to confirm the effectiveness of this treatment, along with studies looking at combining this treatment with other therapies.

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that destroys memory and other important mental functions. AD affects more than 44 million people worldwide and more than six million Americans. Given this prevalence, studying AD is a high priority, and researchers have been searching for better ways to learn more about the disease.

Now, researchers at the Wisconsin National Primate Research Center and other institutions at UW-Madison have shown rhesus monkeys can be a new, translational model for studying late-onset Alzheimer’s disease. “Age is a major risk factor for late-onset Alzheimer’s disease (AD) but seldom features in laboratory models of the disease,” the researchers write in the scientific publication Aging Cell.

The researchers studied brain tissues from transgenic mice, old monkeys with age-related amyloid plaques and post-mortem brain tissue from donors who were aged 72 to 96 and diagnosed with AD after death. This approach provides an alternative to the most common approaches to modeling AD, which tend to use young mice in which plaques and tangles are genetically imposed and seldom include age as part of the study design.

The new study design, however, shows the aged environment impacts inflammatory processes linked to neurodegeneration. In the monkeys and humans, where plaques develop as a function of age, each demonstrated differences from mice in the immediate vicinity of amyloid plaques, but were similar to each other.

In all three species, the authors discovered new structures enriched in mitochondria surround the plaques, and the presence of these plaques influences metabolism. In the monkeys and humans, said Dr. Ricki Colman of the WNPRC, “this mitochondrial dysfunction appears to be suggestive of Alzheimer’s disease.”

The published study concludes that, given the clear parallels between amyloid plaques in monkeys and humans, further studies in nonhuman primate models are warranted. Monkey models are more likely to translate to human disease than mouse studies and could help advance treatments for AD.

Endometriosis is a condition that occurs when patches of the endometrium, a layer of tissue lining the uterus, travel throughout the body and attach to other organs, like the ovaries or intestines. Unfortunately, 1 in 10 women experiences pain and even infertility due to this disorder. Current treatments include surgery to remove the mislocated tissue and drug treatment to suppress ovarian activity, which can lead to weight gain, mood changes and headaches. 

After decades of study, a team of researchers, including Wisconsin National Primate Research Center scientists, discovered a possible new therapy for endometriosis that zeroes in on a particular region of chromosome 7 as the responsible gene. 

A thorough study of the DNA of women in 32 families with deep-rooted histories of endometriosis helped researchers narrow in on this single gene variant – neuropeptide S receptor 1 (NPSR1) – which they found in many, but not all, of the women with more severe cases of endometriosis.  

To learn more about this complex disease, researchers simulated endometriosis in mice by injecting bits of bacteria or uterine lining into their abdomens while attempting to silence the culprit gene. The researchers saw positive results with the rodents experiencing less inflammation and abdominal pain.  

As a next step, researchers will study this same treatment in monkeys, which have been an animal model for endometriosis studies for several decades. Joseph Kemnitz, former director of the Wisconsin National Primate Research Center, explains, “We documented the similarities of endometriosis in our monkeys compared to affected women in collaboration with Stephen Kennedy at Oxford.” The teams recognized the Wisconsin monkeys offered an excellent opportunity to examine endometriosis and have continued building on early results that revealed a familial pattern, suggesting a genetic risk.

As genomic tools continue to advance and analysis costs decrease, the rate of testing treatments stands to increase. Such comprehensive scientific progress is excellent news for the pursuit of improved human health. 

Source: Science Translational Medicine on Aug. 25, 2021. 

Dengue spreads to humans through the bite of an infected mosquito generally living in tropical climates. Symptoms (lasting 2-7 days) commonly seen with dengue include fever, nausea, rash, aches, and pains.

While most people who contract the virus see minimal long-term effects, the Wisconsin National Primate Research Center is studying whether the severity of maternal and fetal Zika virus infection increases in pregnant women who previously had dengue fever.

This first-ever study relating dengue to Zika arose from a concern that a previous dengue infection may become the catalyst leading to more potentially dangerous immune system responses when contracting Zika, especially in pregnant women and their fetuses.

Rhesus macaques were used for the study because their placental development closely mimics humans. Using them as the control, researchers uncovered prior exposure has no measurable impact on Zika replication in maternal plasma. All animal pregnancies resulted in healthy births and infants (in contrast to a small percentage of human infants born to women infected with the disease).

Researchers believe further study to understand the risks of antibody-dependent enhancement to pregnant women worldwide is needed as vaccines against dengue and Zika are developed.

Want to know more about the ongoing fight to eliminate Zika? Here are some additional ways NPRC scientists across the country are making progress against this disease.

Sources: https://www.cdc.gov/dengue/index.html