Feel that familiar tickle in your nose? You may be coming down with the common cold – a virus that has been afflicting humans for thousands of years.

One of the most ubiquitous illnesses, human rhinovirus (HRV) is responsible for more than 50% of cold-like illnesses and billions of dollars annually in medical visits and missed days of work. Yet, despite its prevalence and a nearly 60-year search, there is still no cure for the common cold.

But while most humans recover from the common cold in about seven days, a recent discovery of rhinovirus in chimpanzees resulted in a nearly 10% fatality rate. This is the first time scientists have seen rhinovirus cross the species barrier.

“It was completely unknown that rhinovirus could infect anything other than humans.” said Tony Goldberg, a professor in the University of Wisconsin-Madison’s School of Veterinary Medicine. “It was surprising to find it in chimpanzees, and it was equally surprising that it could kill healthy chimpanzees outright.”

The outbreak occurred in a chimpanzee community in Kibale National Park, Uganda. Of the 56 animals, five chimps between the ages of two and 57 died. A local veterinarian obtained a fecal sample from a deceased chimpanzee, allowing UW scientists to discover that the virus originated from a human cold host.

“We expected to see changes all over the genome,” said Ann Palmenberg, a UW-Madison professor of biochemistry. “But it is not a chimp-adapted virus.”

This discovery means that chimps are genetically predisposed to rhinovirus C, a particularly severe form of the common cold. This virus primarily affects young children with susceptible receptors, or “locks” that allows viruses to enter and infect cells.

“The virus found in Betty (a two-year old chimp) was one that looked like it came from a human, and the level of virus in the lung was comparable to what we see in children,” said James Gern, a Professor of Allergy and Immunology in the UW School of Medicine and Public Health. “There’s a species-wide susceptibility of chimps to this virus,” added Goldberg.

This discovery could have a major impact on scientist and zoologists alike. Goldberg suspects that rhinovirus C may have been overlooked for decades as a cause of chimpanzee death. Now, scientists are more motivated than ever to find a cure to the common cold — both for humans and their counterparts in the wild.

Reviewed August 2019

What causes infertility? The brain, of course.

With the discovery in 2013 that the ovaries weren’t the only producer of estrogen, researchers at the Wisconsin National Primate Research Center (WiNPRC) wanted to know how estradiol, the type produced by the hypothalamus region of the brain, affected the estrogen feedback loop.

This hormonal mechanism is the back and forth communication between the brain, pituitary gland and ovaries that regulates the menstrual cycle. The brain and pituitary gland tell the ovaries to produce estrogen. Estrogen then tells the brain and pituitary gland to release hormones. Those hormones then tell the ovary to release an egg. But after the discovery that the brain also produced estrogen, scientists at the Wisconsin National Primate Research Center wanted to know how these two sources of estrogen interact.

Using rhesus macaques as test subjects, they temporarily stopped their ovaries from producing estrogen. They also implanted a capsule under the monkeys’ skin that would release estradiol. The result? The brain and pituitary gland released only 30 percent of the luteinizing hormone necessary to begin ovulation.

Then, the researchers repeated the process, but this time, they blocked estradiol production in the hypothalamus. But without the estrogen produced by the brain, the hormones weren’t concentrated enough to release an egg.

“The ovarian estrogen starts the [hormone] surge, but the brain estrogen allows the surge to continue,” says Brian Kenealy, a researcher at the WiNPRC.

“This shows the brain’s estrogen is a huge helper, necessary for the release of an egg that makes pregnancy possible,” says Ei Terasawa, a pediatrics professor at the UW-Madison School of Medicine and Public Health and senior scientist at the Wisconsin National Primate Research Center. “We have to modify our concept of the feedback loop.”

For women struggling with infertility, this finding may unlock future treatments. For now, it’s a step forward in our understanding of the estrogen feedback loop.

Reviewed August 2019

There’s no love lost between the cardiovascular system and the world’s population – after all, heart disease is the leading cause of death around the globe. While scientists have long attempted to create vascular models to explore potential causes, preventions, treatments and cures for vascular disease, understanding just how each medical condition arises has hampered potential discovery.

A recent study authored by University of Wisconsin-Madison professor and Wisconsin National Primate Research Center scientist Dr. Igor Slukvin and Akhilesh Kumar, assistant researcher in his lab, might change all of that. Now, scientists are poised to get a better look at the fundamental development of the cells that make up blood vessels and how they can be more reliably cultured in the laboratory dish.

The new scientific advancement provides a blueprint for how vasculature arises at the earliest stages of development, allowing scientists to study the cells that compose blood vessels and devise new models for studying blood vessel disease. Critically, the discovery of methods to generate the building-block cells could set the stage for engineering blood vessels in the laboratory for disease modeling, drug screening and therapeutic purposes.

“Now, investigators will have access to a plethora of new research identifying cell type alternatives for vascular engineering,” said Kumar, noting that the new Wisconsin study, paired with the ability of the progenitor stem cells to proliferate and differentiate to different cell types in culture, can potentially accelerate the time it takes to grow vascular grafts.

Previously, identifying different vascular cell types in living tissue was the easy part; distinguishing cell types from cells grown in culture was a different story. In the study, Kumar made an important revelation – cells that compose blood vessels arise from a common progenitor. The ability to trace the developmental path that gives rise to the cells that make up blood vessels provides science a potent pathway to devise new cellular therapies.

Immediate application of this scientific research includes creating laboratory models for vascular disease to inform a better basic understanding of what goes wrong in killers such as coronary artery disease and certain genetic diseases that affect vasculature. Moreover, these cells can be used in high-throughput drug screens, accelerating the pace of development of new drugs and repurposing old ones to treat vascular ailments. Creating new blood vessels from scratch is still far from reality, but the new Wisconsin study is an essential step toward that goal.

Reviewed August 2019

On February 1, 2016, the World Health Organization declared the Zika virus to be a global health emergency. Spread by the bite of an infected mosquito, the Zika virus has moved rapidly across the Western hemisphere and is linked to potential birth defects.

A team of researchers at the University of Wisconsin-Madison, along with collaborators at Duke University and the University of California, Davis, is working to understand the threat Zika could cause to human pregnancies. Through their work with rhesus monkeys at the Wisconsin National Primate Research Center (WiNPRC), the researchers can uniquely understand the virus’ short and long-term effects.

“There are so many things about Zika infection we can’t study as well in pregnant humans – or fast enough to make a difference for a lot of people who may be infected,” says Dr. Dawn Dudley, a UW-Madison pathology research scientist. “The precise pathway that the virus takes from mom’s bloodstream to the fetal bloodstream, across that interface, cannot be studied except in an animal model.”

The research team, led by primate center scientist Dr. David O’Connor, monitored four pregnant rhesus macaque monkeys that were exposed to the Zika virus. Through regular assessment of maternal infection and fetal development, the researchers found evidence that the virus was passed efficiently to each fetus.

The infection spread inflammatory damage through the tissues that supported the fetus and its developing nervous system, suggesting that the virus poses a larger threat to human fetuses than originally theorized. In fact, three of the fetuses had small heads (although not quite small enough to diagnose microcephaly) and unusual inflammation of the eyes. However, the medical study did not find abnormal brain development.

These sobering results suggest that, as they grow, human babies who were exposed to the virus may develop more Zika-related disease pathology. Research teams are currently working to understand how Zika interacts with other infections, how the effects of early pregnancy infection differ from later infection, and whether antiviral therapies could manage the effects of congenital Zika syndrome.

Reviewed August 2019

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Photo credit: Wisconsin National Primate Research Center

The controversy is over. Consuming fewer calories leads to a longer, healthier life, according to a joint report from the Wisconsin National Primate Research Center and the National Institute of Aging (NIA) on the diets of rhesus monkeys.

This report is the third in a series researching the effect of caloric intake on aging. In 2009, the UW–Madison team, led by primate center scientist Dr. Ricki Colman, reported that rhesus monkeys that ate less had fewer instances of cancer, cardiovascular disease, and insulin resistance. However, a 2012 study from the NIA showed no significant correlation between diet and health. With both teams hungry for an answer, they worked together to reach a more satisfying conclusion.

“These conflicting outcomes had cast a shadow of doubt on the translatability of the calorie restriction paradigm to understand aging and what creates age-related disease vulnerability,” said Rozalyn Anderson, an associate professor of medicine at UW–Madison collaborating with Dr. Colman and others on the study.

After comparing the two independent reports, the research team drew four key conclusions.

• Eating less is more beneficial for adult and older primates than for younger or juvenile animals.
• The number of calories reduced matters. The test group at UW–Madison ate less than the group at NIA and was less at risk for major health issues.
• Less processed food leads to fewer health issues. The NIA primates ate naturally sourced foods compared to the high-fat, sugar-rich diet of those at UW – Madison.
• Comparatively, females are less affected by a fatty diet.

While the two original studies considered caloric intake, they didn’t factor in the effect of age, diet, and sex. It’s those other ingredients, when evaluated alongside calorie count, that make up the complete recipe for healthy living. Energized by this discovery, researchers continue to explore the interaction between calorie count and quality of life.

Reviewed August 2019

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Photo credit: Yerkes National Primate Research Center

14 million – that’s how many women in the United States suffer from Polycystic Ovary Syndrome (PCOS), a crippling disease that that increases  risk of endometrial cancer, heart disease, high blood pressure, type 2 diabetes, asthma, obesity, depression and anxiety. Women with PCOS also experience infertility and a variety of reproductive disorders, resulting in heartbreak for millions of American families.

“With so many different symptoms, it took a long time for physicians to identify the disease as more than infertility,” explains Dr. David Abbott, professor of OB/GYN at the University of Wisconsin-Madison School of Medicine and Public Health who has studied the origins of PCOS at the Wisconsin National Primate Research Center for nearly 30 years.

Yet, despite its widespread reach, PCOS has long stumped scientists. That’s why researchers from the California and Wisconsin National Primate Research Centers, Northwestern University Feinberg School of Medicine and University of California-Los Angeles combined forces to search for causes, preventions, treatments and cures for PCOS.

Each scientist’s decades of experience and research came together in a comprehensive review of 114 articles reporting different PCOS biomarkers. The review also covers overall progress in improving the lives of PCOS patients, including better counseling, managed care and new directions in genetic testing.

For example, a recent study from the Wisconsin NPRC examines testosterone levels in the hair of newborn monkeys. The results reveal that, while PCOS symptoms may not appear until puberty, the disease might actually be programmed in the fetus during the second trimester of pregnancy. Such tests in human infants will allow medical professionals to identify and ameliorate PCOS before onset. Knowledge of its genetic origins and that PCOS may be programmed during intrauterine life allows scientists to explore how the maternal-fetal environment affects female health over generations.

Even after 30 years of continuous research, scientists like David Abbott anticipate much more discovery in the field of PCOS. He notes that, “today, thanks to researchers and doctors working together on all aspects of this problem, many more clinicians cross-refer to one another, and catch more of the specific pathologies that can lead to a PCOS diagnosis and better care.

Reviewed August 2019

Flickering candles, rose petals, smooth music, and… nothing? Many women who are premenopausal experience  inhibited sexual desire, or hypoactive sexual desire disorder, making physical intimacy seemingly impossible – and scientists are unclear as to why. As the drug touted as “the female Viagra” hit the market, researchers at the Wisconsin National Primate Research Center studied more about how the drug, called flibanserin, actually works, which may also lead to ways to improve its safety.

Dr. David Abbott, a professor of obstetrics and gynecology in the University of Wisconsin School of Medicine and Public Health, and Dr. Alexander Converse, associate scientist at UW–Madison’s Waisman Center, studied the effects of flibanserin in the common marmoset. Similar to humans, marmosets rely on pair bonding for mating success and family life. They also exhibit similar hormonal signaling activity and mating behaviors, especially in response to sexual cues such as touch and scent, providing an unparalleled model of the primate brain.

Scientists are especially interested in better understanding flibanserin due to its adverse side effects. These can be serious and include severely low blood pressure and potential loss of consciousness. In addition, alcohol consumption, certain medicines and liver impairment can exacerbate the risks.

To explore flibanserin’s effect on the brain, Abbott and Converse compared flibanserin-treated monkeys to untreated monkeys using noninvasive PET scanning on live common marmosets at the Wisconsin National Primate Research Center. After mapping the animals’ brains with MRI scans, Converse used PET imaging to correlate changes in brain chemistry, particularly the use of glucose at specific locations with flibanserin-induced behavioral changes. Together with colleague Yves Aubert, Converse and Abbott found glucose metabolism declined in the brain center linked to intimate grooming and solicitation of sex.

Study results link flibanserin-initiated decreases in female metabolism to increased pair bonding, meaning the bigger the metabolic dip in brain activity, the more grooming. Although both males and females in the study initiated more grooming, the behavior was more pronounced in the males, even though only females received the drug.

Although the female marmosets did not have hypoactive sexual desire disorder, the study nonetheless shows that flibanserin, by altering metabolic brain activity, prompts increased female behavior responses to grooming, a form of intimate, gentle touching from males. That, said Abbott, “offers the first insight into how the drug may be working in the brains of women.”

Reviewed August 2019

Kids can inherit their parents’ eye color, hair type, and even bone structure. But can genetics also explain a child’s anxiety levels? Researchers from the University of Wisconsin-Madison (UW) investigated whether there is a generational link for anxiety.

The study from UW’s Department of Psychiatry and the HealthEmotions Research Institute examined a large, multi-generational family of nearly 600 rhesus monkeys. Like humans, monkeys can become anxious when exposed to unfamiliar people, environment, or circumstances. In this study, monkeys were exposed to strangers who did not make eye contact – a situation that a human child may encounter.

During this situation, scientists used medical imaging methods commonly used on humans, including positron emission tomography (PET scans) exams, to identify the regions of the brain affected by anxiety. Once these medical images were taken, researchers compared brain activity within the rhesus family tree. The researchers found increased  activity across three parts of the brain 1) the amygdala, 2) the limbic brain fear center, and 3) the pre-frontal cortex.

“Over-activity of these three regions of the brain is directly linked to the later life risk to develop anxiety and depression,” said Dr. Ned Kalin, Wisconsin National Primate Research Center scientist and chair of psychiatry at the UW School of Medicine and Public Health. “This is a big step in understanding the neural underpinnings of inherited anxiety.”

This research marks a breakthrough in adolescent anxiety-related research, as it helps explain how genetics might affect brain function. Indeed, it was found that about 35% of anxiety tendencies can be explained by family history. Moreover, half of children who show extreme anxiety symptoms develop stress-related psychiatric disorders later in life.

“Now that we know where to look, we can develop a better understanding of the alterations that give rise to anxiety-related brain function,” Dr. Kalin said. “Our genes shape our brains to help make us who we are.”

Reviewed August 2019

A lock of hair – it’s not just a keepsake.

For the first time, researchers at the Wisconsin National Primate Research Center have proven an infant’s delicate hairs could reveal the hormonal environment to which the fetus was exposed during gestation. Their methods have significant implications for several fields, from neonatology to psychology, social science to neurology.

“We had this ‘Aha!’ realization that we could use hair in newborns, because it starts growing one to two months before birth,” said Dr. Christopher Coe, UW–Madison professor of psychology and director of the Harlow Center for Biological Psychology.

While hair closest to the scalp reveals more recent information, moving down the shaft effectively transits an individual’s hormonal timeline. For the noninvasive study, researchers took small samples of hair from mother rhesus monkeys and their infants, cleaned them and pulverized the hairs into a fine powder. Scientists then read the hormonal signature using a new mass spectrometry method.

Researchers were particularly interested in hormone differences in infants born to younger, first-time mothers versus more experienced mothers. To test their question, they compared monkey mothers equivalent in age to 15-year-old humans to older monkeys. Scientists have long known maternal age plays a role in pregnancy and delivery outcomes, but evidence suggested something more.

Prior studies have shown high levels of cortisol can impair reflexes and attention and increase incidence of emotional and learning problems. In the monkey study, researchers found that cortisone, an inactive form of cortisol, was higher in young mothers and in their babies than in hair of the older mothers and their infants.

Both Coe and Amita Kapoor, first author of this study and a researcher at the Wisconsin National Primate Research Center, are particularly interested in how maternal age affects the “maleness” and “femaleness” of babies. Additionally, babies born to young mothers also had higher levels of estrone (a form of estrogen) and testosterone in their hair than did babies born to older mothers. Levels of both these hormones were surprisingly similar between male and female infants, raising questions about everything from the significance of birth order to stereotypical “boy” and “girl” behaviors in children.

Scientists studying humans are “really excited because [this method] is so noninvasive,” Kapoor said. Next up? Scientists interested in performing similar tests on humans are looking for answers to a longstanding question – how come human babies aren’t quite as hairy as other primates?

Reviewed August 2019

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

According to the Centers for Disease Control and Prevention (CDC), more than 1 in 10 U.S. school-aged kids have received an Attention Deficit Hyperactivity Disorder, or ADHD, diagnosis. That’s 6.4 million children who struggle with inattentiveness, hyperactivity, and – as Dr. Luis Populin from the University of Wisconsin (UW) studies – impulsive behavior.

“If you say to an impulsive child, ‘Do your homework so you will get a good grade at the end of the quarter,’ that has less appeal than ‘Let’s play baseball this afternoon instead of studying chemistry,’” said Dr. Populin, an associate professor of neuroscience at UW-Madison.

To measure impulsive behavior, Dr. Populin studied rhesus monkeys at the Wisconsin National Primate Research Center who showed signs of ADHD, measuring the effects of methylphenidate (or Ritalin, a common ADHD drug) on their working memory and other aspects of executive functioning.

In the study, monkeys who exhibited calmer behavior learned to wait for a larger, delayed reward, while monkeys who tended to fidget and act nervously always chose the immediate, but smaller incentive. This willingness to take a small reward right away, rather than wait for the larger, delayed reward is called “temporal discounting.”

However, when given doses of methylphenidate, both monkeys chose the delayed reward more frequently, improving the condition of temporal discounting – but perhaps impacting other areas of the brain.

Armed with this information, Dr. Populin hopes to devise a mathematical tool that will help a doctor choose the correct dosage to reduce a child’s impulsive behavior – but not hinder executive function skills.

To continue his research, Dr. Populin was awarded the prestigious Hartwell Individual Biomedical Research Award, which provides research funding for three years. With this funding, Dr. Populin and his team are continuing their study of ADHD, examining kid’s temporal discounting (also known as delay discount and time discounting) while playing computer games.

“We will test temporal discounting with a game that kids don’t see as boring, but is still able to evaluate impulsivity so the doctor can make a faster, more accurate dosage calculations,” said Dr. Populin. “Then everybody benefits.”