In general, as humans, healthy aging impacts our cognitive and affective functions. Our cognitive capacity declines while our emotional lives become more positive and social relationships take a more central role.

The reasons for this are unknown, though scientists suspect it may be because humans have awareness of a limited lifetime. This could possibly lead to a greater interest in maintaining social relationships at the expense of the non-social world in the face of waning cognitive and physical resources.

However, a recent study conducted by researchers at California National Primate Research Center (CNPRC) found humans may be unique in this regard.

The scientists tested whether old rhesus macaques lost interest in non-social stimuli, collecting data from males and females between 4 and 30 years old. Each macaque was tested with a food puzzle outfitted with an activity monitor to evaluate their inclination to manipulate the puzzle in order to gain a food reward. The team found no indication older macaques were less interested in the puzzle than younger ones, nor were they less able to solve it.

These findings suggest there are no significant age-related changes in environmental exploration — at least in rhesus macaques — and indicate there is more research to be conducted to understand such social phenomena across species.

Could increasing just a single type of molecule in the brain alleviate anxiety? According to researchers at the California National Primate Research Center (CNPRC), it could indeed.

Anxiety disorders often emerge around adolescence and can continue to affect people for most of their lives. Researchers can now identify children who display an extreme anxious or inhibited temperament and determine that they are at risk to develop stress-related conditions as they transition to adulthood. However, little is known about how to effectively alleviate anxious symptoms.

CNPRC scientists recently conducted a study examining “dispositional anxiety”—the tendency to perceive many situations as threatening—in nonhuman primates. Researchers used an altered virus to boost levels of a molecule called neurotrophin-3 in the dorsal amygdala of juvenile rhesus macaques.

They found that this increase led to a decrease in anxiety-related behaviors, particularly behaviors associated with inhibition, a core part of the early-life risk for developing anxiety disorders in humans. Brain imaging studies of these animals found that neurotrophin-3 changed activity throughout the brain that contributes to anxiety.

Because current treatments work for only a subset of people and often only partially relieve symptoms, this finding provides hope for new methods of early-life intervention to treat people at risk for anxiety disorders, depression and related substance abuse.

Andrew Fox, an assistant professor in the UC Davis Department of Psychology and a researcher at the CNPRC, hopes that other scientists can further build on their research. The research team included a list of additional promising molecules for future investigation.

“We’re only just beginning,” noted Fox. “Neurotrophin-3 is the first molecule that we’ve been able to show in a nonhuman primate to be causally related to anxiety. It’s one of potentially many molecules that could have this effect. There could be hundreds or even thousands more.”

A new understanding of microbial processes is helping to reveal the cause of ulcerative colitis through the study of a nonhuman primate disorder, idiopathic chronic diarrhea (ICD).

ICD affects 3 to 5 percent of all captive macaque monkeys, and researchers believe wild macaques could be affected at similar rates. ICD is unresponsive to medical intervention and not caused by any particular pathogens.

California National Primate Research Center (CNPRC) scientist Amir Ardeshir, PhD, first began investigating the relationship between microbiomes and intestinal diseases like ICD in macaques—and ulcerative colitis in humans—when he learned of a human patient who had temporarily treated their ulcerative colitis by consuming the eggs of a parasite called Trichuris trichiura.

Ardeshir tried this patient’s home remedy in ICD-affected monkeys and discovered, astonishingly, that the parasite was an effective treatment in four out of five monkeys.

Now, in his latest study, Ardeshir and a team of researchers have found an interesting relationship between the Trichuris parasite and the monkeys’ microbiome—the community of trillions of microbes living on and in primates’ bodies.

The study found that treated monkeys had different microbial communities than healthy control subjects, making them particularly good at building the protective mucosal layer along the intestinal wall. This layer is key in protecting intestinal epithelium from pathogens.

The team of scientists then identified some of the specific bacteria occurring in cases of ICD using a new software called SAMSA2. This software-based approach revealed not only which bacteria were present in each monkey’s gut, but also provided information about what those bacteria were doing and how they might be interacting.

The researchers found a dramatically high number of “bacteria that are very notorious for mucin degradation,” Ardeshir noted. Mucins are glycoproteins which are necessary for the maintenance of the mucosal layer lining human and nonhuman primate intestines. Without it, the mucosal layer and gut bacteria can’t maintain a healthy relationship. Biopsies of human patients with ulcerative colitis show dysfunctional mucosal layers, suggesting this may be the source of irritation and inflammation in both ICD and ulcerative colitis.

Though the exact causes are still unclear, Ardeshir noted that this study brings the field much closer to a full understanding of these types of intestinal bacterial diseases.

Reviewed: June 2020

In 2018, wildfires tore across the state of California, leaving smoldering remains in their wake. These were some of the worst natural disasters on U.S. soil in recent years, and what’s worse, similar occurrences are becoming increasingly common.

If there’s any good to come from these phenomena, it’s that scientists are collecting data in the aftermath that could help reduce the effects of fires on humans and animals. This new research will add to the existing body of knowledge on the subject, including a study originally conducted in 2008 at the California National Primate Research Center (CNPRC). During the study, researchers found altered immunity and lung function in juvenile monkeys that were exposed as infants to wildfire smoke in 2008.

Lisa Miller, leader of the CNPRC Respiratory Diseases Unit, and her team recently tested lung function and blood samples from adult monkeys (now 10 years of age) that were originally exposed to the 2008 wildfire smoke. Their findings were consistent with the earlier study, suggesting that infant exposure to fine particles from fire leads to long term impairment of the respiratory and immune systems in adulthood. 

“The idea behind this is that if we detected any changes in the animals this information might translate as a biomarker that can be used for kids,” said Miller. “The ability of the animals to respond to a real pathogen was reduced. It was a surprise and somewhat disturbing.”

In 2018, smoke from the Butte County Camp Fire—which burned more than 700 square miles—reached the CNPRC, and about 2,000 animals and roughly 500 infant nonhuman primates were exposed for a period of more than 10 days. Because the fires came so close to the UC Davis campus where the CNPRC is located, researchers will once again be able to test the health effects of wildfire smoke on the center’s nonhuman primates. 

Examination of the results is still ongoing, but the additional data from this blaze will help Miller and team continue the search for causes, preventative measures and treatments for the damaging health effects of these massive wildfires.

Reviewed: June 2020

As recent news stories attest, measles is one of the most infectious diseases on Earth — and it affects more than just humans. Nonhuman primates are also at risk.

Although the CNPRC requires all employees and visitors to obtain measles vaccination or show proof of immunity, the center’s animals could still be at risk of outside contamination. Before 1996, the only vaccination protocols for nonhuman primates were based on protocols developed for humans, but these were not cost-effective, and primate facilities needed a better option.

This is why, since 1996, Kari Christe, DVM, has worked to test the safest and most efficient way to vaccinate the entire CNPRC rhesus macaque monkey colony. Her team’s work is also providing information to help other facilities make informed decisions on how to protect their animal colonies.

Christe and her veterinary team have made significant progress. Before this research began, many primate facilities did not have the resources to vaccinate their monkeys. But Christe and team have shown it is possible to protect rhesus macaques from measles in a cost-effective fashion using only half the recommended dose of a specific type of vaccine — the measles and canine distemper vaccine — in comparison to the measles, mumps and rubella vaccine used in humans. The new strategy will save research facilities, zoos and conservation organizations at least $3 per animal (there are nearly 4,000 animals at the CNPRC), based on the most recent estimates. 

With safer and more cost-effective vaccine protocols than ever before, Christe and CNPRC veterinarians are working their way toward protecting all nonhuman primates from measles at their facility and beyond. And this means those same animals will be able to participate in NPRC research studies focused on improving health for humans and animals alike.

Reviewed: June 2020

Working together is always better—especially when it comes to curing infectious diseases. That’s why the National Primate Research Centers (NPRCs) across the country are collaborating to tackle the deadly Zika virus with a series of studies.

In one study, researchers at the California National Primate Research Center (CNPRC) discovered that Zika may still affect fetuses that show no signs of gross microcephaly (an abnormally small head), a common symptom of the disease. Four rhesus macaques were infected with Zika on days 41, 50, 64 and 90 of gestation, respectively. The macaque infected after 41 days experienced fetal death within a week, and the fetuses of the others showed brain calcifications and reduced brain cells—all without significantly reduced brain size.

An additional study at the CNPRC recently showed that infection of the fetuses of pregnant rhesus macaques produced brain lesions like those in human newborns with Zika. The models developed from these studies at the CNPRC can be used across study locations to examine more viruses and prevention methods.

During another study, Zika data from several of the NPRCs were compiled to show that the virus may cause a greater rate of miscarriage than previously thought in humans. Of nonhuman primates infected with Zika in early pregnancy, 26 percent experienced miscarriage or stillbirth even though they showed few signs of infection. Human studies have found that about five percent of women known to be infected with Zika do not carry to term or have stillbirths. This suggests that, in areas where Zika is prevalent, the number of virus-related miscarriages and stillbirths may be underestimated.

These studies show the benefits of taking a highly collaborative approach to research, which is a priority at the NPRCs. Through close communication and teamwork, our researchers are continuing to make breakthroughs to improve worldwide health.

Reviewed: June 2020

Cytomegalovirus, or CMV, is a common virus found in almost every person on the planet. For most of them, it causes no harm and leads to no symptoms. But for newborn babies and people with compromised immune systems, it can lead to birth defects, serious illness and even death.

Now, researchers associated with the California National Primate Research Center (CNPRC) at the University of California, Davis have discovered that low levels of CMV changed microbe and immune cell populations and response to the flu vaccine in rhesus macaques. CMV infection generally increased immune activity but also diminished antibodies responding to influenza vaccination. The study also found that low levels of CMV make the body susceptible to changes in environmental conditions that could accentuate their impact.

“Subclinical CMV infection alters the immune system and the gut microbiota in the host and that impacts how we respond to vaccines, environmental stimuli and pathogens,” said Satya Dandekar, who chairs the Department of Medical Microbiology and Immunology at UC Davis and is a core scientist in the infectious diseases unit at CNPRC at UC Davis. “This study highlights the role of these silent, latent viral infections that are totally asymptomatic.”

The researchers believe that these low-level CMV infections may be one reason for the variation in response to vaccines across large populations. One possibility is that the immune system’s constant effort to control CMV might be diverting resources that it might direct to other threats.

The next step in the process will be testing other vaccines in CMV-infected animals and generally working to better understand how subclinical viruses affect the immune system.

“This highlights the impact silent viruses have to influence how the host responds to vaccines,” said Dandekar. “Can we somehow use this information to optimize our immune system? That’s the direction we would like to go to see how we can inhibit CMV to see if we can enhance the vaccine response.”

Reviewed August 2019

The holy grail of autism research is a reliable test for the condition – and researchers at the California National Primate Research Center (CNPRC), working with colleagues at the Stanford University School of Medicine, have made a promising discovery that may lead to just such a test.

According to the research team, reduced levels of vasopressin – a hormone found in the spinal fluid – may be connected to a reduction in socially acceptable behavior.

“What we consider this to be at this point is a biomarker for low sociability,” said John P. Capitanio, a CNPRC scientist and leader of the Neuroscience and Behavior Unit at the University of California-Davis.

Currently, medical professionals diagnose autism by looking for certain social behaviors. Unfortunately, these tell-tale signs often don’t appear until a child reaches age four or five, limiting opportunities for early treatments that can stem the condition’s progress.

“Right now, the diagnosis is based on parents’ reports of their children’s symptoms, and on clinicians observing children in the clinic,” said Karen Parker, associate professor of psychiatry and behavioral sciences at Stanford and the lead author of the new study.

Researchers looked for autism biomarkers in rhesus macaques, a species whose social capabilities are close to those of humans. The scientists measured levels of two hormones, oxytocin and vasopressin, in their blood and in their cerebrospinal fluid, which bathes the brain.

Monkeys in the less social group had significantly less vasopressin in their cerebrospinal fluid than nonhuman primates in the more social group. In particular, the levels accurately predicted the frequency with which individuals participated in social grooming, an important social activity for this species. Importantly, the team was able to replicate their finding that low vasopressin levels are associated with lower social functioning using a second, independent cohort of monkeys.

The researchers also compared vasopressin levels in seven boys with autism and seven others without the condition. Similar to the results with the rhesus macaques, children with autism had lower vasopressin levels than children without autism.

Moving forward, the researchers plan to test a larger group of nonhuman primates to determine whether the low hormone level can be detected before symptoms of impaired social ability emerge.

Reviewed August 2019

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Photo credit: Kathy West for the California National Primate Research Center

The California wildfires of 2017 are shining a spotlight on research originally conducted back in 2008 at the California National Primate Research Center (CNPRC) which found that exposure to high levels of wildfire smoke negatively affects development of both the immune system and lung function.

Because the fires came so close to the UC-Davis campus where the CNPRC is located, researchers could test the effect of wildfire smoke on the center’s 5,000 nonhuman primates. Since they live outside, they’re exposed to higher levels of smoke than humans. Additionally, the timing of the fire in early summer coincided with the end of the birthing season for rhesus macaques, allowing the researchers to study the effects of the smoke on newborns.

Lisa Miller, leader of the CNPRC Respiratory Diseases Unit, and her team tested lung function and took blood samples from monkeys that were two to three weeks old during the 10 days of peak smoke pollution.

The fine particles found in wildfire smoke can lodge deep in the lungs and are known to cause respiratory illness. This research, however, revealed that exposure in infancy can also impair the development of the immune system. A sample group of the nonhuman primates that had suffered smoke damage were exposed to an infectious disease. Compared to a control group, the immune systems of the doubly-exposed nonhuman primates weren’t as effective at combating the virus.

“The idea behind this is that if we detected any changes in the animals this information might translate as a biomarker that can be used for kids,” said Miller. “The ability of the animals to respond to a real pathogen was reduced. It was a surprise and somewhat disturbing.”

With renewed interest in this research, Miller and others are pressing forward with their work.

Reviewed August 2019

Research from the California National Primate Research Center (CNPRC) is paving the way for future studies where the possibility of birthing gene-edited monkeys that can serve as models for new therapies is greatly increased. CNPRC scientists efficiently used CRISPR/Cas9 technology to modify the genes of rhesus macaque embryos.

Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) is essentially a DNA segment that scientists can manipulate using a system known as CRISPR/Cas9 to edit the genes within organisms. CRISPR/Cas9 seeks and targets specific genes in organisms that are linked to diseases by utilizing a single strand of RNA as a guide to target specific genes for editing.

But the technology can also be imprecise – causing off-target effects to genes that were not intended to be targeted.

“One of the problems with the CRISPR/Cas9 approach is that you have to target the gene,” said Catherine VandeVoort, the core scientist at the CNPRC who collaborated with Keith Latham of Michigan State University and Dr. Daniel Bauer at Harvard Medical School for the study. Latham designed the CRISPR/CAS9 system used in the CNPRC project. “When you have a very short (gene) sequence that you are targeting, it may show up in different places, in another part of the DNA strand instead of where you intend. It can cause off-target effects.”

While rodent-based research models are good for studying diseases in the early stages of research, rodents differ from humans in many anatomical and physiological ways. Alternatively, nonhuman primates share many similarities to humans.

However, while the monkey research model is better for studying human disease, it is much costlier than rodent-based models. “In monkeys, we can’t afford any off-target effects and so we asked ourselves, ‘How can we make this more efficient?’” VandeVoort said.

To minimize the risk of the off-target effects, the study used a two-pronged approach to increase the efficiency of the CRISPR/Cas9 targeting.

The scientists successfully edited the genes of the monkey embryos with 85 percent efficiency. That study demonstrated the first time in the U.S. that this method could effectively be used in monkey embryos. VandeVoort said the embryos used in the study were not implanted in recipient female monkeys, but that a future study will transplant the embryos with a goal of creating a gene-edited monkey.

Reviewed August 2019

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Photo credit: Kathy West for the California National Primate Research Center