A recent study led by Oregon Health & Science University (OHSU) has identified a natural compound that could potentially halt the progression of multiple sclerosis (MS) and certain forms of cancer. The research, published in the Journal of Biological Chemistry, focuses on a plant-derived flavonoid called sulfuretin.

Key findings of the study include:

• Sulfuretin blocks the activity of an enzyme involved in MS and cancer progression.
• The compound inhibits a specific type of hyaluronidase known as CEMIP.
• By inhibiting CEMIP, sulfuretin may prevent the breakdown of hyaluronic acid, which is associated with myelin damage and cancer cell proliferation.

Dr. Larry Sherman, professor at OHSU’s Oregon National Primate Research Center, believes this discovery could have a significant impact on various medical conditions. The research team found that sulfuretin, along with two synthetic compounds, effectively inhibited hyaluronidase activity in live cells.

The study is the result of years of collaborative work between OHSU and the University of Portland, where undergraduate students under the guidance of Dr. Angela Hoffman screened numerous plant compounds. This discovery validates the students’ diligent efforts and highlights the importance of undergraduate research in scientific breakthroughs.

While the results are promising, further testing in animal models is necessary to determine the compound’s effectiveness and potential side effects in treating cancer and neurodegenerative conditions like MS.

This research opens new possibilities for treating a range of disorders, including osteoarthritis, skin infections, and brain injuries caused by heavy alcohol use. As the study progresses, it brings hope for improved treatments for MS, cancer, and other conditions related to hyaluronic acid breakdown.

Scientists at the California National Primate Research Center (CNPRC) have harnessed the power of machine learning, a branch of artificial intelligence (AI), to track anxiety-related behaviors in monkeys. Published in Nature’s Translational Psychiatry, the study demonstrated a significant link between nervous temperament in infant monkeys, as assessed by human observers, and later brain activity and behavior, as measured using machine-learning techniques. These findings suggest a strong connection between early-life nervousness and the eventual development of anxiety and depressive disorders. 

Anxiety disorders, the most prevalent mental illnesses in the United States, impact nearly 20% of the population, disproportionately affecting women. Despite the availability of treatments, over half of those suffering do not seek help. Andrew Fox, a core scientist at CNPRC, believes this research could pave the way for preventing these disorders before they fully develop. 

The Study 

Fox, along with graduate student Dan Holley, utilized cutting-edge technology to monitor anxiety-related behaviors in 18 preadolescent female monkeys. Initially, human observers assessed the monkeys’ temperaments—identifying traits such as confidence, nervousness, and timidness. Two to three years later, the same monkeys underwent brain imaging while participating in behavioral tests designed to assess anxiety-related behaviors. 

Traditionally, this type of experiment required multiple trained researchers to review each video meticulously to quantify behavior. Holley, however, developed a machine-learning technique to automate this process, significantly accelerating the research. “The hope is that machine learning will largely liberate researchers to focus on more interesting and appealing aspects of this work,” Holley explained. 

Key Findings 

The machine-learning approach revealed a strong correlation between infants identified as nervous and a specific anxiety-related behavior known as freezing, where the monkeys remained immobile for at least three seconds. This behavior was linked to increased metabolic activity in the central nucleus of the amygdala, a brain region crucial for threat processing. This finding replicated a relationship identified by researchers at the Wisconsin National Primate Research Center, suggesting the robustness of this connection across different environments. 

Fox and Holley were struck by how accurately human observers could predict future behavior based on early temperament assessments. “When humans were making those observations, they were picking up something about the animal that we have not fully characterized,” Fox noted. 

Future Implications 

The study’s success has already led to funding for further research involving a larger cohort of 159 monkeys, both male and female. 

“Ultimately, our hope is that by understanding the biology, we will be able to develop new behavioral or pharmacological treatments that could help alter the developmental trajectory of individuals with increased inhibited temperament during infancy, preventing the development of anxiety disorders that cause suffering later in life,” Fox said. 

What This Means 

This study marks a significant advance in understanding the long-term impacts of early-life anxiety. By integrating machine learning into behavioral research, CNPRC scientists have opened new avenues for exploring and potentially mitigating anxiety disorders. The team’s innovative approach and promising results highlight the potential for AI-driven tools to revolutionize mental health research and treatment strategies. 

In a groundbreaking leap towards a new Parkinson’s disease treatment, a stem cell therapy company has initiated a clinical trial involving human patients following the success of a novel therapeutic delivery method in non-human primates at the Wisconsin National Primate Research Center. This advance could revolutionize how we treat Parkinson’s disease. 

What is Parkinson’s? 

Parkinson’s disease is characterized as a condition that progressively impairs movement due to the loss of dopamine-producing neurons in the brain. Dopamine is a neurotransmitter crucial for coordinating movement. This leads to symptoms such as rigidity, slowness and tremors. While medications like L-DOPA can temporarily alleviate these symptoms, the drugs often lose effectiveness over time and can cause complications. 

A New Approach with Monkeys  

Researchers at the Wisconsin National Primate Research Center at the University of Wisconsin–Madison have successfully grafted dopaminergic neuronal progenitor cells into the brains of cynomolgus macaque monkeys. These cells, provided by Aspen Neuroscience, were grown from human induced pluripotent stem cells, or iPS cells. The process involved precise surgical techniques guided by intraoperative MRI, allowing for targeted delivery of the cells to areas of the brain most affected by the disease. 

The Human Connection 

The promising results in monkeys paved the way for human trials. The research highlighted the potential of using a patient’s own iPS cells to avoid immune rejection, a significant hurdle in cell therapy. This method not only aims to replace  

lost neurons but also to enhance the patients’ quality of life by reducing symptoms of depression and anxiety associated with Parkinson’s. 

Bridging the Gap to Human Trials 

The transition from animal models to human trials required meticulous planning and collaboration. The study tested different angles for cell delivery to minimize surgical risks and improve recovery times. The findings were crucial in obtaining approval from the FDA to start human trials, marking a significant step forward in the quest to find safe and effective treatments for Parkinson’s. 

Hope for the Future 

As the first human trials commence, this research not only represents a scientific breakthrough but also a sign of hope for improving the lives of millions suffering from Parkinson’s. The journey from lab to clinic underscores the power of innovative science and collaboration in tackling complex health challenges. 

A groundbreaking study from Tulane University has revealed that an experimental cancer drug may hold the key to clearing HIV from infected cells in the brain. This discovery, published in the journal Brain, marks a significant step forward in the fight against HIV and its associated neurological complications. 

Key Findings 

Researchers at the Tulane National Primate Research Center found that a cancer drug significantly reduced levels of SIV (the nonhuman primate equivalent of HIV) in the brain. The drug works by targeting and depleting specific immune cells that harbor the virus. 

Dr. Woong-Ki Kim, lead author and associate director for research at the center, emphasized the importance of this research in addressing brain-related issues caused by HIV, which persist even in patients on effective antiretroviral therapy (ART). 

Why This Matters 

While ART has transformed HIV from a terminal illness to a manageable condition, it doesn’t completely eradicate the virus. HIV persists in “viral reservoirs” in the brain, liver, and lymph nodes, where current treatments struggle to reach. The brain, protected by the blood-brain barrier, has been particularly challenging to treat. 

The Study 

The research team used a small molecule inhibitor called BLZ945 to block a receptor that increases HIV-infected macrophages in the brain. This approach successfully reduced the viral load, essentially clearing the virus from brain tissue. The study involved three groups of subjects, including an untreated control group and two groups treated with different doses of BLZ945. The high-dose treatment led to a 95-99% decrease in viral DNA loads in the brain. 

Looking Ahead 

The next step for researchers is to test this therapy in combination with ART, potentially paving the way for more comprehensive strategies to eradicate HIV from the body entirely. This study, funded by the National Institutes of Health, offers new hope for improving the quality of life for those living with HIV-related neurocognitive problems. As we continue to make strides in HIV treatment, this Tulane study represents a promising step towards tackling one of the most persistent challenges in HIV care – clearing the virus from its hard-to-reach reservoirs in the brain. 

Recent research conducted at the California National Primate Research Center (CNPRC) has uncovered fascinating insights into the perception of touch in nonhuman primates, shedding light on how our brains process pleasurable sensations. Led by Ph.D. Candidate Joey Charbonneau and CNPRC core scientist Eliza Bliss-Moreau, the study investigates the neural responses to gentle, pleasurable touch. Given that the animals were anesthetized, researchers were surprised to find that the brain activity in monkeys mirrored that of humans experiencing pleasant touch. 

Published in the Proceedings of the National Academy of Sciences, the study unveils age-related differences in touch perception, sparking intriguing questions about consciousness and the brain’s processing of tactile stimuli. Understanding these mechanisms not only illuminates fundamental aspects of neuroscience but also has implications for various human conditions, from autism spectrum disorder to neurodegenerative diseases like Alzheimer’s. 

Using functional magnetic resonance imaging (fMRI), researchers examined the brain activity of monkeys who were anesthetized in response to slow, pleasurable touch (also known as affective touch) and faster, discriminative touch (referred to as discriminative touch). Remarkably, they found that the same brain regions activated from pleasurable touch in awake humans and monkeys who were not awake. This suggests that the rewarding aspects of affective suggests that touch transcend species boundaries and do not necessarily require consciousness. 

Moreover, the study identified age-related changes in how touch is represented in the brain, particularly in regions associated with affective processing. Older monkeys exhibited alterations in brain activity patterns to discriminative but not affective touch, highlighting the importance of considering age-related factors in understanding touch perception. 

Nonhuman primates serve as invaluable models for studying touch perception, offering insights that could inform additional research. By leveraging this model, researchers aim to understand the mechanisms underlying touch perception across the lifespan and develop interventions for age-related diseases impacting affective processing. 

This pioneering work, supported by the National Institute of Health and other funding sources, represents a crucial step toward unraveling the mysteries of touch perception and its implications for human health and well-being. 

Research in nonhuman primates is opening new possibilities for testing treatments for early-stage Alzheimer’s disease and similar conditions before extensive brain cell death and dementia set in. A recent study published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association reveals a six-month window during which disease progression can be tracked and treatments tested in rhesus macaques. 

“This is a very powerful translational model to test interventions that target the tau protein,” said John H. Morrison, professor of neurology at the University of California, Davis, and California National Primate Research Center, and corresponding author on the paper. 

 The Role of Tau Protein in Alzheimer’s Disease 

The tau protein, found in neurons, is implicated in Alzheimer’s disease, frontotemporal dementia, and other dementias. Misfolded tau disrupts essential brain cell functions, spreading through connected regions of the cortex that are crucial for memory and cognition. This leads to an inflammatory response and eventually neuron death. 

Advances in brain imaging, biomarkers in human serum and cerebrospinal fluid, and rodent models have improved our understanding of early-stage Alzheimer’s. However, the relationship between tau, inflammation, and disease progression remains complex. The macaque model bridges the gap between mouse models and human patients, better representing the disease’s progression. 

The Six-Month Window for Disease Progression 

In the study, researchers injected a vector carrying DNA for two mutated tau proteins into the entorhinal cortex of 12 monkeys. This brain region, involved with memory, is where Alzheimer’s typically originates in humans. Over six months, they tracked the spread of tau protein, affected cells, and inflammation using PET and MRI imaging, biomarkers, and microscopy. 

The results indicate a window of at least two to six months where disease progress can be measured, allowing for preclinical testing of interventions targeting the tau protein. “We can look at drugs targeting early-stage Alzheimer’s before dementia develops,” Morrison said. “It’s all about early intervention to arrest progression.” 

This study builds on earlier work at the CNPRC establishing the nonhuman primate model. Future research will combine the tau model with existing systems based on amyloid, further enhancing our understanding and treatment of Alzheimer’s disease. 

Every day, the seven National Primate Research Centers (NPRCs) conduct and enable collaborative research studies to improve human and animal health. For more than five years now, we’ve been sharing our latest news and scientific advancements with you via NPRC.org and @NPRCnews (X), and there’s more coming your way. 

To ensure the NPRCs provide the topics of most interest to our readers and followers, we looked back at your favorite stories to help us move forward. Your top interests span behavior and psychology, infectious disease and neuroscience and brain disorders research. We will continue to share news that represents what you have most enjoyed, and we will also bring you information that reflects the breadth and depth of research across the NPRC network.   

We appreciate our readers and followers, and encourage you to take another look at your favorite blogs about NPRC research, to share the information with your family, friends and colleagues, and to continue connecting with us via NPRC.org, @NPRCnews and, now, on the new NPRC LinkedIn account. Via these resources, you’ll always be able to access the latest news on NPRC research that is helping people across generations and around the world live longer, healthier lives.   

Behavior and Psychology 

1. The Effects of Wildfire Smoke Exposure in Early Pregnancy 

A study by California NPRC and UC Davis researchers investigated the effects of wildfire smoke exposure on infant monkeys during early pregnancy. The study found that exposure led to increased inflammation, reduced stress response, memory deficits and a more passive temperament in the monkeys. The findings suggest environmental changes during pregnancy can have lasting effects on offspring.  

Infectious Disease 

2. A Deadly Relationship: Stopping the Progression of Tuberculosis in HIV Patients   

Researchers at the Southwest National Primate Research Center have discovered chronic immune activation in the lungs plays a crucial role in the progression of tuberculosis (TB) and HIV co-infection. This dysfunction hampers the body’s ability to fight off infections. The study suggests the need to develop treatments targeting chronic immune activation alongside antiretroviral therapy (ART). TB and HIV are global pandemics that reinforce each other, affecting a significant portion of the world’s population. The findings offer hope for improved treatment strategies in the next decade. 

3. New Possible Correlation Between Lyme Disease and Lewy Body Dementia  

At Tulane National Primate Research Center, researchers discovered intact spirochetes of Borrelia burgdorferi, the bacterium that causes Lyme disease, in the central nervous system of a 69-year-old woman who received multiple rounds of antibiotic treatment. The presence of this bacterium coupled with her persistent neurological decline raises the possibility of a correlation between Lyme disease and Lewy body dementia. This finding highlights the bacterium’s persistence despite targeted therapy and emphasizes the need for further research to comprehend its role in severe neurological conditions. 

4. Are DNA Vaccinations a Perennial Answer to the Flu?  

Researchers at the Washington National Primate Research Center are developing a universal flu vaccine that could protect against all strains of the influenza virus. Using a DNA vaccine administered through the skin, the team has achieved promising results in macaques, providing 100% protection against a previous flu virus. This approach could eliminate the need for annual flu shots and be quickly deployed during pandemics. The researchers believe this technology could also be effective against other viruses and outbreaks. 

Neuroscience & Brain Disorders 

5. Past Social Experiences May Affect Brain’s Response to Oxytocin

A study at the Emory (formerly Yerkes) National Primate Research Center and Emory University showed the response of neurons to oxytocin, a chemical involved in social bonding, can vary based on an individual’s past experiences. Using female prairie voles, the researchers examined the nucleus accumbens, a brain region related to pair bonding. They found that oxytocin reduced neuron firing before bonding and increased it afterward, when triggered. The study also revealed a connection between oxytocin signals and endocannabinoids, affecting defensive interactions. These findings provide insights into how prior experiences influence oxytocin’s impact on brain circuits. 

6. NPRC Study May Have Found Link That Causes Anxiety and Depression  

Researchers at the Wisconsin National Primate Research Center and the University of Wisconsin-Madison have discovered brain pathways in juvenile monkeys that could contribute to anxiety and depression later in life. By studying the connections between specific brain regions, they found a correlation between synchronization and anxious temperament. These findings may lead to better treatment approaches and help identify gene alterations associated with anxiety. 

7. The Drinking Gene: Could Alcoholism Be Inherited?  

Research conducted at Oregon National Primate Research Center has identified a gene, GPR39, as a potential target for developing medication to prevent and treat alcoholism. By modifying protein levels encoded by this gene in mice, the researchers observed a significant reduction in alcohol consumption. They also found a link between alcohol and the activity of this gene. The study draws attention to the importance of cross-species approaches to identify drugs for treating alcohol use disorder. Further investigations are under way to determine if the same mechanism applies to humans. These findings offer potential insights for developing drugs to address chronic alcoholism and mood disorders. 

Oxytocin is a hormone that plays a critical role in social bonding and attachment. In recent years, researchers have been studying the effects of intranasal oxytocin, a non-invasive treatment that reduces social impairment in several neurological and behavioral disorders, such as autism.  

However, the long-term effects and efficacy of the treatment are currently under examination. Studies conducted by Dr. Karen Bales’ lab at the California National Primate Research Center reveal that chronic intranasal oxytocin produces sex-specific biological and behavioral responses in titi monkeys, a monogamous nonhuman primate.  

The researchers found that all OT-treated monkeys engaged more in social interactions but differed in their social behavior by sex. The males exhibited more social interest in unfamiliar animals, while females directed their interest toward their parents.  

The monkeys were divided into two groups: one received a daily dose of intranasal OT, while the other received saline for six months. The treatment group exhibited more prosocial behavior in their home enclosure immediately following their dose than the control group. 

Researchers also examined neural effects and social behavior during adolescence and into adulthood one-year after treatment ended. As adults, males from the treatment group maintained some prosocial effects. They also scored higher on several measures of affiliative behavior than the control group. Females, however, experienced a slight delay in forming a bond with their new mate. 

The researchers observed that chronic treatments during adolescence altered their behavior long-term, and these behavioral changes were different for males and females. These findings emphasize the complexity of the treatment and lay an essential foundation for more research on its use in humans. 

A collaborator on the project, Dr. Suma Jacob from the University of Minnesota Medical School, explained that “there is more research to be done on oxytocin, how it works, its effects, and feedback systems.”

Oxytocin, a brain chemical known for promoting social bonding and nurturing behavior, has been used in several studies to potentially treat disorders such as autism, but with inconsistent results. 

Yerkes National Primate Research Center Division Chief Larry Young and his research colleagues in Yerkes’ Division of Behavioral Neuroscience and Psychiatric Disorders as well as Emory’s Center for Translational Social Neuroscience found the dynamic response of neurons to oxytocin may vary depending on the past social experiences of the individual. 

The study was conducted in female prairie voles because they form lifelong bonds with their partners and focused on the nucleus accumbens because it plays an important role in the brain for pair bonding. Tissue from the nucleus accumbens was exposed to TGOT, a drug that mimics oxytocin signals. 

Robert Liu, PhD, professor of biology and director of Emory’s Neuroscience graduate program compared the electrical responses of neurons to oxytocin signals to an analog television, before and after the television is tuned to a station. “Before the animal forms a pair bond, oxytocin reduces the static noise: the neurons in the nucleus accumbens fire spontaneously less often,” said Liu. “But after an animal has been exposed to a partner, it increases the clarity of the signal from the station: the neurons gradually fire with greater strength – but only when electrically triggered.”

In an unexpected turn, researchers found that after bonding, oxytocin signals became coupled to endocannabinoids, molecules produced within the brain resembling the psychoactive substances found in cannabis. By blocking the endocannabinoids, the scientists could interfere with some aspects of the prairie voles pair interactions. 

Blocking endocannabinoid signals increased the likelihood the female vole would display a defensive upright posture, a sign of rejection, in the presence of their partner, but not toward a stranger. However, the pair-bonded animals still spent more time with their partner than a stranger. This reaction shows endocannabinoid signaling is modulating defensive interactions, rather than pair bonding. 

The study suggests the way oxytocin modulates brain circuits changes with prior experience, which may help explain inconsistent results from human studies involving oxytocin.

Alzheimer’s disease (AD) is a progressive, neurodegenerative disease that destroys memory and other important mental functions. AD affects more than 44 million people worldwide and more than six million Americans. Given this prevalence, studying AD is a high priority, and researchers have been searching for better ways to learn more about the disease.

Now, researchers at the Wisconsin National Primate Research Center and other institutions at UW-Madison have shown rhesus monkeys can be a new, translational model for studying late-onset Alzheimer’s disease. “Age is a major risk factor for late-onset Alzheimer’s disease (AD) but seldom features in laboratory models of the disease,” the researchers write in the scientific publication Aging Cell.

The researchers studied brain tissues from transgenic mice, old monkeys with age-related amyloid plaques and post-mortem brain tissue from donors who were aged 72 to 96 and diagnosed with AD after death. This approach provides an alternative to the most common approaches to modeling AD, which tend to use young mice in which plaques and tangles are genetically imposed and seldom include age as part of the study design.

The new study design, however, shows the aged environment impacts inflammatory processes linked to neurodegeneration. In the monkeys and humans, where plaques develop as a function of age, each demonstrated differences from mice in the immediate vicinity of amyloid plaques, but were similar to each other.

In all three species, the authors discovered new structures enriched in mitochondria surround the plaques, and the presence of these plaques influences metabolism. In the monkeys and humans, said Dr. Ricki Colman of the WNPRC, “this mitochondrial dysfunction appears to be suggestive of Alzheimer’s disease.”

The published study concludes that, given the clear parallels between amyloid plaques in monkeys and humans, further studies in nonhuman primate models are warranted. Monkey models are more likely to translate to human disease than mouse studies and could help advance treatments for AD.