September 17, 2019

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

August 4, 2016

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

December 10, 2015

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

April 15, 2014

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

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

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