Most of us enjoy listening to our favorite tunes while in the car or relaxing at home—but could music serve an even deeper purpose in our lives?

In September, Larry Sherman, PhD, a professor in the Division of Neuroscience at the Oregon National Primate Research Center (ONPRC) at Oregon Health & Science University (OHSU), joined OHSU research scientists Marc Freeman, PhD, and Erick Gallun, PhD, for an on-stage discussion about research exploring the importance of music for brain development and healing. The researchers were accompanied by internationally-renowned opera singer Renée Fleming.

Sherman, who has performed a series of talks explaining how listening and practicing music can influence brain development and delay cognitive decline in aging, said the soaring feeling of inspiration when we’re playing, singing or listening to music is rooted in brain chemistry. He cited research which has shown magnetic resonance imaging (MRI) reveals a spike in endorphins and dopamine among people exposed to music, which generates a feeling of belonging and of community.

Fleming added that one of the latest iterations of music therapy involves forming drumming circles for people struggling with addiction. Gallun suggested this technique may be soothing because the drumming echoes a rhythm from the earliest possible point of the brain’s development.

“When you’re in the womb, there are only a few things you can hear,” Gallun said. “One is your mother’s heartbeat.”

Fleming recently spent two hours in an MRI machine as part of a Sound Health initiative supported by National Institutes of Health (NIH) to study the specific neural circuits involved in the interaction between music and the brain. She believes that music can have a therapeutic effect, especially for underserved youth populations struggling with social and mental health issues.

“Music can really make a difference in their lives,” she said.

Reviewed: June 2020

Batten disease is a rare and fatal genetic neurological condition that affects the ability of cells to process waste materials. Those materials build up in brain cells and result in a range of symptoms including seizures, vision loss, motor and speech difficulty, slowed learning and personality changes. Eventually, children with Batten disease become blind, wheelchair-bound and bedridden, having lost all their cognitive function. Most affected children die in their early teens.

Researchers at the Oregon National Primate Research Center (ONPRC) at OHSU have discovered a naturally occurring disease in Japanese macaques that mimics the progression of Batten disease in humans. The finding holds promise for developing gene therapies to treat the disease. Human clinical trials could start within five years.

Trevor McGill, PhD, research assistant professor of ophthalmology in the OHSU School of Medicine, said the discovery will accelerate the development of new gene therapies for Batten disease.

“It affects small children and it’s fatal,” McGill said, “and we’ve got the necessary tools in hand here at OHSU to fix it.”

A multidisciplinary team of veterinarians and scientists at ONPRC made the discovery and confirmed that a small population of Japanese macaque monkeys carries a genetic mutation that causes one form of the disease. It’s the only known model for the disease among nonhuman primates in the world.

“This has truly been a collaborative effort, bringing together the expertise of clinical veterinarians and pathologists, scientists with collective expertise in primate behavior and genetics as well as brain and retinal degeneration,” said Anne Lewis, D.V.M., PhD, head of pathology at the primate center.

“The discovery of this nonhuman primate model of Batten disease will advance our ability to develop and test a gene therapy strategy to replace the normal version of the protein that is missing in this disease,” said Jodi McBride, PhD and assistant professor of neuroscience at ONPRC.

Additionally, she said, this new discovery also opens up promising avenues for developing biomarkers of the disease’s progression using advanced imaging techniques such as MRI and PET scanning.

“We don’t have great imaging biomarkers for this disease aside from the gold standard of MRI and so we’re also interested in using this new model to develop imaging techniques that will allow us to determine how successful we are at clearing out the buildup of cellular debris in the brain with potential treatments.”

The ONPRC scientists said that their goal is to quickly develop interventional strategies that can be used to help treat the children suffering from this devastating and fatal disease and offer hope to their families.

Dr. Nancy Haigwood, director of the Oregon National Primate Research Center, discusses the launch of nprc.org, the public-facing website of the seven National Primate Research Centers, in this podcast from Oregon Health and Science University. The website’s goal, she says, is to give the general public information about research at the NPRCs that is “helping humans live longer, healthier lives.”

Researchers at the Oregon National Primate Research Center (ONPRC) have developed a new form of gene correction that will prevent the transmission of genetic disorders from mother to child, which may lead to a “revolutionary way” to treat inherited diseases. Dr. Shoukhrat Mitalipov and his 15-person lab are using a gene-editing technique that involves spindle transfer from the affected egg to the donor egg to address these heritable conditions.

The gene-editing technique described in this study, employed together with in vitro fertilization or IVF, could provide a new avenue for people with a known heritable disease-causing genetic mutation to eliminate the risk of passing the disease to their children. It could also increase the success of IVF by increasing the number of healthy embryos.

Dr. Mitalipov concedes his stem cell research has been controversial for some people, while many others see the human health benefits. “We produce stem cells using eggs. That’s always a controversial issue — where are you going to get eggs?” he said. “Even though egg donation to the reproductive field is a pretty standard procedure, [use of these eggs to generate] stem cells [has] always been questioned.”

While admitting there are concerns about how to ensure there’s no misuse of this scientific technology, “since these families clearly can benefit, I think it’s ethical we allow it,” Dr. Mitalipov said. “At the same time, if there are concerns that a clinic can use it for an unintended use, it can be regulated.”

However, he doesn’t think the technology will be misused. “There is no other nonmedical use for this technology,” he said. “It’s all toward the defective mitochondria and correcting it. In the U.K., they decided it case by case, at least at the beginning. Each family and IVF clinic has to submit an application. Something like that can be done here as well.”

In the United States, 64 percent of women of reproductive age are overweight and 35 percent are obese. New research at the Oregon National Primate Research Center (ONPRC) links an unhealthy diet during pregnancy to mental health disorders, such as anxiety and depression, in children.

The study, led by Dr. Elinor Sullivan, an assistant professor in the Division of Neuroscience at ONPRC at OHSU in Portland, Oregon, tested the effect of a maternal high-fat diet on nonhuman primates, tightly controlling their diet in a way that would be impossible in a human population. The study revealed behavioral changes in the offspring associated with impaired development of the central serotonin system in the brain. Further, it showed that introducing a healthy diet to the offspring at an early age failed to reverse the effect.

Previous observational studies in people had correlated maternal obesity with a range of mental health and neurodevelopmental disorders in children. The new research demonstrates for the first time that a high-fat diet, increasingly common in the developed world, caused long-lasting mental health issues for the offspring of nonhuman primates. “It’s not about blaming the mother,” said Dr. Sullivan.

“It’s about educating pregnant women about the potential risks of a high-fat diet in pregnancy and empowering them and their families to make healthy choices by providing support. We also need to craft public policies that promote healthy lifestyles and diets.”

Researchers assigned a total of 65 female Japanese macaques into two groups, one given a high-fat diet and one a control diet during pregnancy. Then they measured and compared anxiety behavior among 135 offspring and found that both males and females exposed to a high-fat diet during pregnancy exhibited greater incidence of anxiety compared with those in the control group. The scientists also examined physiological differences between the two groups, and found that exposure to a high-fat diet in early development impaired the development of neurons containing serotonin, a neurotransmitter that’s critical in developing brains.

Sullivan believes the findings provide evidence that mobilizing public resources to provide healthy food and pre- and post-natal care to families of all socioeconomic classes could reduce mental health disorders in future generations.

The World Health Organization estimates that about 225 million women in developing countries would like to delay or stop childbearing but are not using any method of contraception.

Dr. Jeffrey Jensen of the Oregon National Primate Research Center is working to develop a low-cost, safe and highly effective method of nonsurgical permanent contraception that will meet the needs of women in low-resource regions, but also be of interest to women in resource-rich countries.

“When women have completed their family size, or wish to not have children, many prefer a noninvasive, effective and permanent form of birth control,” said Jensen. “Particularly in low-resource settings where there is no choice but to continue bearing children, women benefit greatly from a safer form of permanent contraception.”

“Many of the patients I see have had good success with reversible contraception methods, but still desire a permanent method,” he continued. The only permanent form of contraception currently available to women is tubal ligation, which “requires, at a minimum, one counseling visit, one pre-operative visit, and one half-day in the day surgical unit or procedure room. The inconvenience and time burden for my patients provides a strong motivation for me to come up with a better approach.”

Dr. Jensen believes that the approach to permanent contraception should be the same for women in lesser developed as in more developed nations. To be acceptable in regions with low resources, like sub-Saharan Africa, women and health care providers need to know that a method is safe and well-accepted by well-to-do women in resource-rich nations, he says.

With a grant from the Bill & Melinda Gates Foundation, Jensen launched the Oregon Permanent Contraception Research Center at the Oregon National Primate Research Center.

Jensen’s team uses nonhuman primates to study nonsurgical approaches to permanent contraception for women, because of the unique anatomic features and reproductive physiology they share with women. Using the baboon model, Jensen’s research has demonstrated that transcervical administration (similar to the placement of an IUD) of a single dose of polidocanol foam can result in a high rate of tubal occlusion and prevent pregnancy. The addition of doxycycline may improve efficacy, and refinements of the approach to demonstrate safety are in progress as the team hopes to transition the research into early phase clinical trials in women.

Updated August 2019

The rapid spread of the Zika virus has led to widespread media and government attention; however, little is known about the disease itself. How long does the disease stay in the system? Where does the Zika virus attack? And how does it spread to offspring?

A team of interdisciplinary researchers from OHSU in Portland, Oregon, is attempting to find these answers. Collaborating with the Oregon National Primate Center (ONPRC), the team is beginning to unlock the mysteries of the virus – and ultimately pave the way for future therapies and vaccines.

“This study helps us better understand how the virus manifests itself so that scientists can develop therapies and vaccines that would work in humans,” says Dr. Daniel Streblow, Associate Professor of Molecular Microbiology and Immunology in the OHSU Vaccine and Gene Therapy Institute, OHSU School of Medicine. “Our study significantly advances what is known about the growth of the virus in the host.”

The research team, a 20-person cross-section of faculty across the university, examined the Zika virus infection in seven rhesus macaques from March 2016 to August 2016. The study observed the Zika virus at seven, 28 and 35 days post-infection.

Ultimately, it was found that the Zika virus attacks tissues in the nervous system, male and female reproductive and urinary tracts, muscles, joints and lymph nodes. The virus first presents itself as a rash, fever or pink eye, and then persists in the body for at least 35 days.

“What is different about this research is that we also were able to look at specific points in time to see where the virus grew in the tissues so we can identify and target the reservoirs where the virus hides,” says Dr. Streblow.

This medical study was conducted in response to the Zika virus outbreak across the Western hemisphere. In 2016, there were 5,102 reported cases of the Zika virus in the United States, and an additional 36,079 cases reported in US territories.

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

Only one individual in history has been cured of HIV. This person is known as “the Berlin patient,” named for the location where the renowned HIV-ridding procedure took place. Scientists at the Oregon National Primate Research Center (ONPRC) at OHSU are working to understand how a specific mutation in a gene may block HIV infection in the host. Using CRISPR technology, researchers are creating the same mutation and bone marrow transplantation performed on that patient to study how it might play a role in HIV infectivity.

Jon Hennebold, professor and chief, Division of Reproductive & Developmental Sciences, at ONPRC, said that Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR) genome-editing technology is responsible for these new insights. “You can’t fully study HIV in rodent models because it’s a primate-tropic virus,” he said. CRISPR is essentially a programmable molecular scissors that scientists can manipulate 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.

“This technique exploded in the scientific community about five years ago, so it’s relatively new,” Hennebold said. “Basically, CRISPR works by cutting the DNA in the target gene of interest, which in turn results in the creation of a mutation at that site when the cell repairs the gap in the gene,” Hennebold said. “It doesn’t do it randomly. It goes to a gene of interest and will cut the DNA at that point.” Further, “It was a huge advance from the standpoint of being able to modify genomes, so it could be used to modify many different organisms’ genomes. Previously, you were only able to do that in a few models. You could never apply the previous approaches to organisms other than mice.”

In addition to work with HIV, CRISPR is currently being used to help researchers understand conditions such as blindness, autism, and neurodegenerative diseases that are too complex to be studied in a rodent research model.

Menopause isn’t always accompanied by physical symptoms. In fact, for many women, the side effects of this hormonal change aren’t quite as tangible as hot flashes and stiff joints. A decline in mental faculties such as reasoning and perception can often occur. However, a study from the Oregon National Primate Research Center suggests that hormone therapy may mitigate such cognitive changes.

For the nonhuman primates treated with estradiol implants, both spatial working memory and visuospatial attention improved throughout the course of the one-year testing period compared to those receiving a placebo. While post-menopausal hormone therapy has been a frequent topic of debate, the research supported the hypothesis that estradiol treatment is a sustainable solution for managing symptoms.

“There have been several previous studies published on the effect of hormone therapy on cognition in the nonhuman primate, with equivocal results,” said lead author Dr. Steven G. Kohama, a neuroscientist at the Oregon NPRC. “However, in comparison to these earlier reports, our study was much longer, and it suggests a sustained benefit from early intervention after menopause with hormone treatment.”

As the pro-hormone therapy argument grows stronger, the list of research questions grows longer. Researchers are already considering whether treatment earlier in menopause slows cognitive decline more than therapy introduced later.

An estimated 15.1 million adults in the United States have Alcohol Use Disorder (AUD), a chronic brain disease characterized by compulsive alcohol use. This includes approximately 6.2 percent of all American adults, a staggering percentage of drinkers nationwide.

“The amount of alcohol consumed in the US is not only substantial, but unequally divided in terms of who drinks how much,” said Dr. Kathleen Grant, Chief and Senior Scientist of Behavioral Neuroscience at the Oregon National Primate Research Center (ONPRC). “A small proportion drink the vast majority of alcohol sold.”

But why can some people safely enjoy a single nightcap, while others are at risk for developing alcoholism or a serious alcohol problem?

Dr. Grant hopes to answer that very question by studying a population of rhesus monkeys. Through her research, she is unraveling why some people are at a greater risk for heavy drinking habits.

Dr. Grant studies monkeys who have been exposed to alcohol over the course of three months. Like humans, some choose to drink water, some choose to drink alcohol, and some choose to drink a combination of the two. Understanding why certain monkeys choose to drink alcohol heavily provides clues as to why some humans are at a higher risk for developing a drinking problem.

Dr. Grant has found that males – both monkeys and humans – are more likely to become problem alcohol drinkers than females. In addition, monkeys that are exposed to stressful situations or stimuli choose to drink alcohol more than those that are not.

However, there are several risk factors that affect humans, but are not seen in monkeys. For example, in humans, family history of alcoholism can affect one’s inherited genes and environment and ultimately lead to an increased risk of heavy drinking. In addition, drinking alcohol between the ages of 13-15 increases the lifetime chances of being diagnosed with alcohol dependence.

Ultimately, Dr. Grant hopes her research will help identify those at risk for developing alcoholism before they’ve developed an alcohol addiction. By determining certain biomarkers in the brain and blood, she is hopeful that, eventually, we can caution people that they’re heading toward addiction before it begins.

“Prevention would be so much better for everyone because alcoholism affects more than just the individual,” Dr. Grant said.

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