It may seem counterintuitive, but could cutting back on calories help us preserve the body’s capabilities as we age?

According to new research from the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin (UW) School of Medicine and Public Health, monkeys on calorie-restricted diets age better than monkeys on a normal diet.

This is the latest in a series of papers from the Aging and Calorie Restriction Study based at WiNPRC. The series first garnered attention 10 years ago, when the improved survival and health benefits of calorie restriction were initially reported.

In the latest study, there were two groups of aged rhesus monkeys—one on a normal diet and another on a fully nutritionally complete diet with 30 percent fewer calories.

The scientists found that muscle mass was up to 20 percent better preserved in the calorie-restricted monkeys, and muscle quality also improved. These benefits were linked to better muscle function, more efficient movement and better diabetes risk profiles like blood glucose levels and insulin sensitivity.

“It’s all about metabolism,” said Associate Scientist Timothy Rhoads, PhD. “Not just in the muscle tissues themselves, but more broadly at the systemic level, too”.

Associate Professor of Medicine Rozalyn Anderson echoed his sentiments.

“Calorie restriction (CR) preserves muscle quality and physical function in monkeys, and our work connects this specifically to metabolism—how energy is derived, stored and used,” she said.

Researchers at the NPRCs across the country are helping to demystify the aging process. For additional reading, check out this recent study from the California National Primate Research Center (CNPRC), which examined the changing social habits of aging primates.

Is it possible for consciousness to be controlled through the brain? And if so, what implications could this have for people with serious brain disorders or conditions, like comas?

As it turns out, a small amount of electricity delivered at a specific frequency to a particular point in the brain will wake a nonhuman primate out of deep anesthesia, according to a study by a team led by researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW).

Macaques put to sleep with general anesthetic drugs commonly administered to human surgical patients, propofol and isoflurane, were revived and alert within two or three seconds of applying a low electrical current.

“For as long as you’re stimulating their brain, their behavior — full eye opening, reaching for objects in their vicinity, vital sign changes, bodily movements and facial movements — and their brain activity is that of a waking state,” said Yuri Saalmann, UW-Madison psychology and neuroscience professor. “Then, within a few seconds of switching off the stimulation, their eyes closed again. The animal is right back into an unconscious state.”

Mice have been roused from light anesthesia before with a related method, and humans with severe disorders have improved through electric stimulation applied deep in their brains. The new study, however, is the first to pull primates in and out of a deep unconscious state.

In the study, the scientists focused on a spot deep in the core of the brain called the central lateral thalamus. Lesions in that area of the human brain are linked to severe consciousness disruptions, such as comas.

As the macaques moved from unconscious to conscious states, the researchers observed the central lateral thalamus stimulating parts of the cortex, or the outer folds of the brain. In turn, the cortex influenced the central lateral thalamus to keep it active, forming a loop—or an engine—of sorts.

Achieving this manipulation of consciousness in the brain required precisely stimulating multiple sites as little as 200 millionths of a meter apart simultaneously, as well as applying bursts of electricity 50 times per second. The researchers noted that designing and delivering electrical stimulation with such precision gives them hope that their approach could be used to help patients dealing with many types of abnormal brain activity.

 “We can now point to crucial parts of the brain that keep this engine running and drive changes in the cerebral cortex that affect your awareness, the richness of your conscious experience,” explained Saalmann.

The inner workings of the brain are complex and have yet to be fully unraveled, but scientists at the NPRCs are making daily progress in helping us to understand this fascinating and crucial organ. You can learn more about the other NPRC neuroscience studies here.

In the midst of the novel coronavirus (COVID-19) outbreak, scientists at the National Primate Research Centers (NPRCs) have initiated research programs to better understand and diagnose as well as develop potential treatments and vaccines for the disease. NPRC animal colonies will be key in moving SARS-CoV-2 infection/COVID-19 research from cell models to studies in whole living systems so researchers can determine treatment safety and effectiveness.

Since the virus began to spread at the end of 2019, more than 3 million people have been infected worldwide as of April 28, 2020, with numbers growing daily. The coordinated efforts of the scientific community will be crucial to slow the spread of COVID-19, lower the risk of transmission and treat those who have the disease.

NPRC COVID-19 Research

Several of the NPRCs have made public announcements that research is under way, including California NPRC, Southwest NPRC, Tulane NPRC and Wisconsin NPRC. Others, including Oregon, Washington and Yerkes NPRCs, are also beginning research, and Oregon and Yerkes are accepting applications for COVID-19 pilot projects, which facilitate research collaborations and provide important preliminary data.

California NPRC researchers have already isolated, characterized and cultured COVID-19 from a patient treated at UC Davis, the first community-acquired case in the U.S. Next, they plan to make diagnostic tests in-house.

The Southwest NPRC scientists are proposing research projects to establish a nonhuman primate model to study the development and transmission of the disease, test new detection methods and partner with others in the scientific community.

At Tulane NPRC, researchers plan to create a nonhuman primate model to study the disease’s clinical progression, how it is transmitted through the air and how it specifically affects aging populations. The scientists are aiming to answer many questions, including why older individuals are more susceptible to complications and death from COVID-19.

In Wisconsin NPRC researchers have developed a coalition of scientists to combat the disease, drawing heavily from their firsthand experience during the Zika virus outbreak in 2016.

Yerkes NPRC researchers have begun initial research, and the center’s goals include understanding immunity and antibody response to SARS-CoV-2, and developing diagnostics, key reagents, antiviral therapies and vaccines.

COVID-19 Research Safety

The NPRCs are well-positioned to conduct SARS-CoV-2 infection/COVID-19 research because of our expertise in infectious diseases and collaborations internally at each NPRC as well as across NPRCs and with colleagues worldwide. Also, we can conduct such research safely in our Biosafety Level 3 (BSL3) facilities specifically designed to keep personnel, the research and the environment safe. Examples of BSL3 safety features include additional training and oversight for employees, directional air flow and filtered ventilation systems, and specialty equipment to contain the virus isolates used in the research and to decontaminate the lab space and research equipment and supplies.

News Stories about NPRC COVID-19 Research

Recent news articles by STAT News, Bloomberg, The Scientist and ABC News provide more information about the NPRC studies and the critical role of research with animals.

As we have more information to share about NPRC COVID-19 research, we’ll post information at NPRC.org/news and tweet from @NPRCnews. In the meantime, here are a few helpful COVID-19 resources we’re following.

At the NPRCs, our focus is conducting research and caring for our irreplaceable animal colonies so we can help people and animals live healthier lives. In the midst of the global COVID-19 pandemic, we are prioritizing our research to focus on developing diagnostics, preventions and treatments for this novel disease.

As we work to combat this health crisis, we also want to help keep you informed about the latest developments. Below are some of the resources we are following. These organizations are on the front lines of combatting COVID-19 and are frequently sharing crucial information regarding public health, personal guidelines and coronavirus research.

Centers for Disease Control and Prevention (CDC)
https://www.cdc.gov/coronavirus/2019-ncov/index.html
https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

World Health Organization
www.who.int/emergencies/diseases/novel-coronavirus-2019

National Institutes of Health
https://www.nih.gov/health-information/coronavirus

In addition, we want to provide resources to help address any mental health and emotional well-being concerns COVID-19 brings for you and your loved ones:

CDC’s Recommendations for Managing Anxiety and Stress
https://www.cdc.gov/coronavirus/2019-ncov/prepare/managing-stress-anxiety.html

National Alliance on Mental Illness
https://www.nami.org/About-NAMI/NAMI-News/2020/NAMI-Updates-on-the-Coronavirus

Just for Kids: A Comic Exploring the New Coronavirus
https://www.npr.org/sections/goatsandsoda/2020/02/28/809580453/just-for-kids-a-comic-exploring-the-new-coronavirus

The NPRCs are working closely with our collaborators worldwide to address COVID-19. Look for updates from us at NPRC.org and @NPRCnews.

When preparing for motherhood, no mom-to-be should have to worry about a potentially life-threatening illness. And thanks to the work of researchers at Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin-Madison (UW), we’re one step closer to controlling a disease which exclusively affects pregnant women.

Preeclampsia raises a mother’s blood pressure, threatening both her life and her baby’s. Symptoms usually include water retention and protein in the urine, as well as rarer and more severe effects like liver or kidney failure.

The disease is treatable if detected early and handled with regular prenatal care, but no one knows its cause or how to prevent it. However, two studies by WiNPRC researchers have offered promising insights.

In one study, researchers discovered testosterone levels in preeclamptic women are elevated two to three times above normal levels. Animal models of preeclampsia also showed patterns and levels of increases in testosterone mimicking those found in women. This correlated positively with vascular dysfunction and higher placental androgen (hormone) receptor gene expression.

In a closely related study, scientists using an animal model found maternal vascular adaptation to pregnancy is critical for blood flow through the placenta to the developing baby. If vasculature can’t properly adapt, the mother may develop preeclampsia and other hypertensive disorders.

These discoveries could help scientists create life-saving treatments.

“With these confirmed animal models of preeclampsia, we can now dig deeper to uncover the etiology and pathogenesis of preeclampsia to gain a better understanding of the disorder and advance treatments and preventions for women,” explained David Abbott, Ph.D., of WiNPRC.

While no true cure for HIV/AIDS exists, patients can suppress the virus through a continuous regimen of medication. But now, scientists have discovered a new approach to dealing with HIV infection—one which could eliminate the need for such ongoing treatment.

The study was conducted at the Wisconsin National Primate Research Center (WiNPRC) with the University of Miami (UM) Miller School research team, the Frederick National Laboratory for Cancer Research in Maryland and the Gene Therapy Center at the University of Massachusetts Medical School.

In the study, researchers used an adeno-associated virus (AAV) to deliver gene products into the muscle cells of nonhuman primates, turning the cells into “factories” which produce genetically engineered antibodies indefinitely.

One primate in the study had an exceptionally positive response to the new approach. After receiving a single injection of the AAV-delivered antibodies, its HIV viral load immediately dropped below the limit of detection and has remained undetectable for more than three years.

According to Ronald C. Desrosiers, PhD, professor of pathology at UM and a longtime HIV researcher, this result provides proof of concept that this approach can deliver a functional cure for HIV.

“Our goal is to be able to deliver these potent broadly neutralizing antibodies with one shot so the patient is good for life,” he explained. “But more research needs to be done.”

While such a technique—known as anti-retroviral drug therapy— may suppress viral replication in HIV-infected humans, or SIV- or SHIV-infected monkeys, the study’s authors say it is not a cure. Removal of antiviral drugs results in a rebound of plasma viral loads in the vast majority of individuals. Because of this, repeated infusions are needed to maintain a protective concentration.

In addition, while two other monkeys in the study also maintained long-term viral suppression, the AAV delivery method triggered a defensive immune system response which inactivated the antibodies. The muscle cell-produced antibodies were seen as foreign antigens, resulting in an anti-drug reaction, which can also occur in some patients receiving antibodies for treating Crohn’s disease, rheumatoid arthritis or other conditions.

“Now, we have to solve this anti-drug antibody problem so that we can generate a robust response in virtually all humans,” said Desrosiers, noting this could be a significant breakthrough for world health. “One advantage to this AAV approach is that it could be readily applied throughout the developing world, where antiretroviral therapies are not readily available. An easy ‘one-shot’ approach could make a huge difference in addressing this global epidemic.”

Rhesus macaques have long been considered the prime model for AIDS vaccine research because these monkeys’ immune systems are analogous to humans.

In fact, most medications approved to treat HIV in humans to date have resulted from biomedical research with macaques, much of it performed at the National Primate Research Centers.

Now, for the first time, scientists have used a genetically engineered herpesvirus to achieve significant vaccine protection against the AIDS virus in monkeys. Only live attenuated strains of simian immunodeficiency virus (SIV) – the monkey version of HIV – have previously provided similar protection.

This finding, supported by multiple NIH grants, comes from research at the University of Miami and the Wisconsin National Primate Research Center (WiNPRC). Lead researcher Mauricio Martins is an assistant professor working with long-time AIDS vaccine research experts and NPRC collaborators Ron Desrosiers and David Watkins in the Department of Pathology, Miller School of Medicine, University of Miami.

Although several approaches to an AIDS vaccine show promise, molecularly cloned SIVmac239 is difficult for antibodies to neutralize, just as HIV-1 is in human infection, and a variety of approaches have had great difficulty achieving protective immunity against it, the authors reported.

“These latest results demonstrate for the first time significant protection against acquisition of SIVmac239 by any vaccine regimen other than live-attenuated SIV vaccines,” said Martins.

Four out of six vaccinated monkeys were protected against infection following repeated viral injections over four months, whereas five out of six control animals became infected over the same time span — and those five acquired it the most quickly of all the animals. Animal care and humane euthanasia were administered throughout this study by WiNPRC veterinarians as needed and under the guidelines of the American Veterinary Medical Association.

The herpesvirus used in the study was rhesus monkey rhadinovirus (RRV). The genetically engineered strain, rRRV-SIVnfl, produced not only replicating RRV, but noninfectious SIV, both working together to elicit a safe and strong enough response to fight off SIV infection. It is crucial for any prophylactic vaccine to recognize and kill all virus particles before they invade T-helper cells, take over their machinery and create more viruses. In AIDS, when those viruses eventually burst out, they kill their host cells, destroy the rest of the immune system and eliminate the body’s defenses against lethal opportunistic infections.

Further work is needed, the authors say, to define the critical components necessary for eliciting this protective immunity, evaluate the breadth of the protection against a variety of strains, and explore how this approach may be extended to humans.

Photo credit: National Institute of Allergy and Infectious Diseases

It has been known that a widely-used attention-deficit/hyperactivity disorder (ADHD) drug affected the brain—but the specifics of those effects hadn’t been fully understood until now.

Luis Populin, PhD, professor of neuroscience in the School of Medicine and Public Health at the University of Wisconsin-Madison, and colleagues at the Wisconsin National Primate Research Center (WiNPRC) have demonstrated for the first time the complete actions of Ritalin (methylphenidate, or MPH) on various regions and chemicals in the brain.

Ritalin can increase dopamine, a brain chemical associated with reward-motivated behavior, and is typically prescribed to children with ADHD. This increase changes the way the brain makes connections among its various networks, including those that affect attention, learning and motor processes.

In the study, the scientists used positron-emission tomography (PET) imaging to study the brains of three conscious adult male rhesus monkeys. Using simultaneous functional magnetic resonance imaging (fMRI), the researchers were able to directly link increases in dopamine from MPH to changes in functional connections between the caudate—the part of the brain critical to learning through storing and processing memories—and the prefrontal, hippocampal and motor regions.

Studies in humans using fMRI have explored how MPH alters the brain, but some of those studies have reported increases in dopamine after MPH administration, while others have reported decreases. The researchers noted that this may be because most studies used a single dose of the drug and different experimental conditions.

In this study, they “bridged the gap” between neurochemistry and functional organization by simultaneously measuring changes in extracellular dopamine using PET. Additionally, the doses given to the monkeys were comparable to those resulting in equivalent blood levels of the medication when used therapeutically in children.

“Our study sheds much needed light on understanding the mechanisms underlying the effects of therapeutically relevant doses of MPH,” said Populin, adding that future studies may go even further to understand how the drug works in the context of cognition. “We hope we can expand on this research to better understand how the drug works in the brain while it’s actually processing different things.”

Populin noted that the more scientists discover about the processes, the more effective doctors can be in prescribing ADHD medications for children.

Parkinson’s Disease is a complicated neurological illness, the causes of which are still not fully understood by the scientific community. Researchers at the Wisconsin National Primate Research Center (WiNPRC), however, recently made a discovery that could serve as a useful piece of the proverbial Parkinson’s puzzle.

The WiNPRC scientists conducted a study that found phosphorylated alpha-synuclein—a modified version of a protein common to nerve cells—in tissue samples from common marmosets with inflamed bowels. This type of chemical alteration is similar to abnormal protein deposits in the brains of Parkinson’s patients, which suggests that inflammation may play a key role in the development of the disease.

“It’s not entirely clear what its function is, but the typical version of the protein alpha-synuclein occurs normally in all neurons,” explained Marina Emborg, a professor of medical physics in the UW School of Medicine and Public Health. “A lot of neurodegenerative disorders seem to be related to the aggregation of certain proteins.”

In addition, people who suffer from inflammatory bowel disorders are more likely to be diagnosed with Parkinson’s, further bolstering the evidence that inflammation and oxidative stress may be involved in the disease.

“The colon, the gastrointestinal tract overall, has this dense network of nervous tissue, the enteric nervous system, which is sometimes called the gut brain,” said Emborg. “This has lots of neurons, and those neurons—like all neurons—have alpha-synuclein.”

 “(This study) shows us the relationship between inflammation and Parkinson’s-like alpha-synuclein pathology,” she continued. “It doesn’t mean if you have inflammatory bowel disorder, you will get Parkinson’s. The development of a neurodegenerative disorder is multifactorial. But this could be a contributing factor.”

We’ve all heard the phrase “Mr. Mom” as a descriptor for involved fathers, but men may be more like their female counterparts when it comes to nurturing than we expect.

Most animals are risk-averse and tend to avoid danger, but parents can be a different story. Certain species of mammals will even risk their own lives to save their offspring.

This extreme bond between parent and child has its roots in a biological phenomenon known as “bonding.” When children are born, their mothers experience a rush of hormones designed to facilitate the bonding experience, including oxytocin, estrogen, progesterone and others.

Perhaps the most interesting hormone released during this process is prolactin, which stimulates lactation in new mothers to feed their offspring. It is intriguing not only because of its physical effect on mothers, but because it also appears in (and influences) their mates as well.

Researchers at the Wisconsin National Primate Research Center (WiNPRC) at the University of Wisconsin (UW) have discovered male tamarins and marmosets—which live in family units like those of humans—display certain physical characteristics when their respective mates become pregnant.

“The father is critical to the survival of the offspring,” Toni Ziegler, distinguished scientist at the WiNPRC, said of the animals during an interview on a recent BBC Earth podcast.  “And what we know about them from our studies, is the father is picking up on cues from the mother that she’s pregnant. And the father actually starts gaining weight.”

Ziegler noted this is consistent with human males, who frequently report gaining “sympathy weight” when their partners become pregnant.

This discovery could potentially lead to a better understanding of the bonding process and what can be done to nurture the infant-parent relationship from birth into early childhood.