Global warming is breaking a 400-year climate link between two oceans

  A new study suggests that the climate connection between the tropical Indian and Pacific oceans can be disrupted by major volcanic eruptions, while human-caused greenhouse gas emissions may now be driving an even more unusual breakdown in that relationship.

Researchers at the Woods Hole Oceanographic Institution (WHOI) combined paleoclimate evidence with climate model simulations to examine how closely the two ocean basins have behaved over the past several centuries.

Their findings indicate that volcanism can temporarily weaken the climate link between the Indian and Pacific oceans. More recently, however, human-driven climate forcing has produced what the researchers describe as an "exceptional" shift in the way climate variability in the two regions is connected.

The study was published in Nature Communications under the title "Coupling of Pacific and Indian Ocean variability disrupted by 19th century volcanism."

A Climate Connection That Usually Moves in Step

Climate conditions across the Indian Ocean often respond to changes occurring in the Pacific Ocean. This connection helps shape broad patterns of rainfall, temperature, and atmospheric circulation across the tropics.

Since the 1980s, however, scientists have noticed that this relationship has weakened. The Indian Ocean has increasingly behaved differently from what would normally be expected based on conditions in the Pacific, a change that researchers have linked to climate warming.

One challenge is that reliable instrumental climate records cover less than a century. That makes it difficult to determine whether the recent change is truly unusual or simply part of a longer natural cycle.

To look further back in time, the WHOI team turned to tropical paleoclimate records preserved in corals, tree rings, and stalagmites. These natural archives allowed the researchers to reconstruct Indian and Pacific Ocean climate conditions back to the early 1600s.

Volcanoes Disrupted the Ocean Link in the 1800s

The paleoclimate evidence shows that the Indian and Pacific oceans remained closely connected through most of the past 400 years.

One period stood out.

Between 1810 and 1850, the relationship between the two ocean basins changed significantly. Researchers linked that disruption to a series of major tropical volcanic eruptions, which appear to have weakened the Pacific Ocean's usual influence over climate conditions in the Indian Ocean.

Computer simulations covering the past thousand years supported that interpretation.

The strength of the disruption depended on both the size of the volcanic eruptions and the background climate conditions that existed at the time.

"This is one of the first studies to examine the breakdown in the connection between the Pacific and Indian oceans using evidence from past climates, modern observations, and climate models," said co-author Caroline Ummenhofer, a senior scientist at WHOI.

Modern Changes Appear Far More Unusual

The volcanic connection was only part of what the researchers uncovered. By comparing the modern climate with several centuries of past conditions, they were also able to judge how unusual the current weakening of Indian and Pacific Ocean coupling really is.

"The modern data we have is limited and doesn't go back far enough. With climate models and paleo-records, we are now able to say with more confidence that the recent changes we are seeing are really quite exceptional," said lead author Shawn Wang.

Wang is a former WHOI graduate student and postdoctoral researcher, and he is currently a postdoc at the University of Colorado Boulder.

The findings suggest that although volcanic eruptions can temporarily interrupt the connection between the two ocean basins, the modern breakdown appears to be driven by a different force.

"A key finding is that global warming and human emissions are now overwhelming the Pacific's natural influence on the Indian Ocean," Ummenhofer said.

Why the Indian Ocean Matters for Climate Predictions

Understanding how strongly the Indian and Pacific oceans influence each other is important for climate forecasting.

Connections between ocean basins can help scientists anticipate shifts in rainfall and other major climate patterns. If those relationships weaken or change, forecasts based on historical behavior may become less reliable.

Much past research has examined major ocean basins separately. This study instead focuses on the ways they interact, and on what happens when those connections begin to weaken.

Source: ScienceDaily

Scientists find hidden pathways pancreatic cancer uses to spread

 A new study from Brazil, published in the journal Molecular and Cellular Endocrinology, sheds light on how pancreatic cancer gains the ability to spread at an early stage. Researchers found that a protein called periostin, along with stellate cells in the pancreas, plays a crucial role in helping cancer cells invade nearby nerves. This early nerve invasion raises the risk of metastasis and is closely tied to how aggressive the disease becomes. The findings also highlight potential targets for more precise and personalized cancer treatments.

The research shows that pancreatic tumors do not act alone. Instead, they alter parts of the surrounding healthy tissue, effectively reprogramming it to support cancer invasion. This process helps explain why pancreatic cancer is so difficult to control once it begins to spread.

A Rare Cancer With a Deadly Impact

The most common form of pancreatic cancer is adenocarcinoma, which develops in the glandular cells that produce pancreatic juice. This type accounts for about 90% of all pancreatic cancer diagnoses. While pancreatic cancer is not among the most frequently diagnosed cancers, it is known for being especially aggressive. Its death rate nearly matches its diagnosis rate.

Worldwide, there are roughly 510,000 new pancreatic cancer cases each year, with nearly the same number of deaths reported annually.

In Brazil, estimates from the National Cancer Institute (INCA) point to about 11,000 new cases and 13,000 deaths each year. "It's an aggressive cancer that's difficult to treat. Around 10% of patients have a chance of long-term survival, such as five years after diagnosis," says Pedro Luiz Serrano Uson Junior, an oncologist and one of the study's authors.

Why Nerve Invasion Matters

One reason pancreatic cancer is so dangerous is a process known as perineural invasion. This occurs when cancer cells move into and spread along nerves. The process can cause severe pain and also helps the tumor reach other parts of the body more easily. "Perineural invasion is a marker of cancer aggressiveness," Uson explains.

Because nerves connect different regions of the body, cancer cells that enter these pathways gain new routes for expansion.

Mapping the Tumor's Hidden Support System

The research was carried out at the Center for Research on Inflammatory Diseases (CRID), one of FAPESP's Research, Innovation, and Dissemination Centers (RIDCs). The study was led by researcher Carlos Alberto de Carvalho Fraga, with Helder Nakaya serving as principal investigator. Nakaya is also a senior researcher at Einstein Israelite Hospital and a professor at the University of São Paulo's School of Pharmaceutical Sciences.

To uncover how nerve invasion occurs, the team used advanced tools that analyze the activity of thousands of genes in individual cells while mapping their exact locations within tumor tissue. "We were able to integrate data from dozens of samples with extremely powerful resolution," Nakaya says.

The researchers examined 24 pancreatic cancer samples and found that the stroma, the connective tissue that supports the tumor, plays an active role in cancer progression rather than serving as a passive structure.

The Role of Periostin and Tissue Remodeling

One of the study's most important findings involved pancreatic and stellate cells that produce large amounts of periostin. This protein is known for its ability to reshape the extracellular matrix - the structure that organizes and maintains healthy tissue.

Tumor cells rely on major changes to this matrix in order to push through tissue and reach nearby nerves. This remodeling process involves specialized enzymes and widespread tissue disruption. "Periostin participates in this remodeling, paving the way for tumor cells to invade," Nakaya explains. Once cancer cells reach a nerve, it can act like a "road" that helps them spread further.

Why Treatments Struggle to Reach the Tumor

As the tumor environment changes, it triggers a desmoplastic reaction. This involves the buildup of dense, fibrous tissue around the tumor, made up of cells and proteins that stiffen and inflame the area. The hardened tissue makes it harder for chemotherapy and immunotherapy drugs to penetrate the tumor.

This protective microenvironment allows cancer cells to survive and continue spreading. "That's why pancreatic cancer is still so difficult to treat," says Uson.

Early Spread Leads to Poor Outcomes

According to Uson, the tumor's ability to infiltrate surrounding tissue is a major reason for the poor outlook faced by many patients. "Perineural invasion is a sign that cancer cells have gained mobility. They escape the tumor mass, travel through healthy tissue, and reach nerve and lymphatic bundles, which carry them to other regions of the body, facilitating the development of metastases."

More than half of pancreatic cancer cases already show signs of perineural invasion at an early stage. However, this spread is usually discovered only after surgery. "Unfortunately, we discover this perineural invasion after it's already occurred. It's only seen in the surgical specimen when it goes for biopsy," Uson says.

Source: ScienceDaily

Scientists find the genetic switch that makes pancreatic cancer resist chemotherapy

 Researchers at Duke-NUS Medical School have discovered a molecular "switch" that determines whether pancreatic cancer cells respond to chemotherapy or resist it. The finding points to a way to potentially shift some of the most treatment resistant tumors into a state where existing drugs can work more effectively.

The study, published in the Journal of Clinical Investigation, explains how this switch operates at a molecular level. The results suggest that pairing targeted therapies with standard chemotherapy may improve outcomes for patients whose tumors no longer respond to treatment.

Why Pancreatic Cancer Is So Difficult to Treat

Pancreatic cancer is one of the deadliest cancers worldwide. In Singapore, it ranks as the ninth most common cancer but the fourth leading cause of cancer related death. Because symptoms often appear late and current treatments have limited impact, most patients depend on chemotherapy, which typically provides only modest benefit.

Over the past decade, scientists have identified two main molecular subtypes of pancreatic cancer, classical and basal. Tumors in the classical subtype tend to be more organized at the cellular level, and patients with this form are more likely to respond to treatment. In contrast, basal subtype tumors are more disorganized and aggressive, and they are often resistant to chemotherapy.

Importantly, pancreatic cancer cells are not fixed in one subtype. They can shift between these states, moving from a more treatable form to a more resistant one. This flexibility is known as cancer cell plasticity.

The Role of GATA6 in Tumor Behavior

The research team focused on a gene called GATA6, which helps maintain pancreatic cancer cells in the more structured and less aggressive classical state. When GATA6 levels are high, tumors tend to grow in a more organized way and are more likely to respond to chemotherapy. When GATA6 levels fall, cells lose that structure, become more aggressive, and are harder to treat.

Professor David Virshup of Duke-NUS's Programme in Cancer & Stem Cell Biology, the study's lead author, said:

"We have known that pancreatic cancer cells can switch between these two states. What we didn't understand was the mechanism driving that switch. By identifying the pathway that suppresses GATA6, we now have a clearer picture of how tumors become resistant -- and potentially how to reverse that process."

KRAS and ERK Pathway Drive the Switch

The researchers traced the switch to a chain of signals inside pancreatic cancer cells. A gene called KRAS, which is mutated in nearly all pancreatic cancers, sends constant growth signals that drive tumor development. KRAS passes these signals through a partner protein known as ERK, which relays the instructions further inside the cell.

When the ERK pathway becomes highly active, it protects another protein that interferes with the production of GATA6. As GATA6 levels drop, cancer cells lose their organized structure, shift toward the more aggressive basal state, and become much less responsive to chemotherapy.

Using genetic screening, molecular analysis in cancer cells, and drug treatments, the team demonstrated that blocking the KRAS and ERK pathway lifts this suppression. When that happens, GATA6 levels rise again. The cancer cells then shift back toward the more organized state and regain sensitivity to chemotherapy.

Combination Therapy Shows Stronger Effects

The study also found that higher levels of GATA6 on their own made pancreatic cancer cells more responsive to treatment. When drugs that inhibit the KRAS and ERK pathway were combined with standard chemotherapy, the anti cancer effects were stronger than with either approach alone. However, this enhanced benefit occurred only when GATA6 was present, highlighting its central role in determining which patients might benefit most from combination therapy.

These findings help clarify why patients with higher GATA6 levels often respond better to certain chemotherapy regimens. They also provide a scientific foundation for ongoing clinical trials that are testing new treatments aimed at KRAS and related pathways.

Professor Lok Sheemei, Duke-NUS' Interim Vice-Dean for Research, said:

"Pancreatic cancer remains one of the toughest cancers to treat. These findings provide a mechanistic explanation for why tumors respond poorly to chemotherapy and offers a rational strategy for combining targeted therapies with existing drugs."

Broader Implications for Other KRAS Driven Cancers

The implications may extend beyond pancreatic cancer. Many other cancers fueled by KRAS mutations show similar shifts in cell behavior and treatment response. Understanding how cancer cells transition between different states could help researchers address therapy resistance in additional cancer types.

Professor Patrick Tan, Dean and Provost's Chair in Cancer and Stem Cell Biology at Duke-NUS, commented:

"This work demonstrates how basic science can uncover actionable insights into treatment resistance. Understanding how cancer cells switch states gives us a more strategic way to design combination treatments."

Duke-NUS Medical School is internationally recognized for its leadership in medical education and biomedical research, combining fundamental discoveries with translational expertise to improve health outcomes in Singapore and beyond.

Source: ScienceDaily

Scientists discover sleep switch that builds muscle, burns fat, and boosts brainpower

 Deep sleep does more than help you feel rested. It actively rebuilds your body, strengthening muscles, supporting bone growth, and helping burn fat. For teenagers, it is also essential for reaching full height potential.

At the center of all this is growth hormone, which surges during sleep. But scientists have long puzzled over why poor sleep, especially the early deep stage known as non-REM sleep, leads to lower levels of this critical hormone.

Scientists Discover the Brain Circuit Behind It

Researchers at the University of California, Berkeley, have now uncovered the answer. In a study published in Cell, they mapped the brain circuits that control growth hormone release during sleep and identified a new feedback system that keeps those levels in balance.

This discovery offers a clearer understanding of how sleep and hormones work together. It may also open the door to new treatments for sleep disorders linked to metabolic diseases like diabetes, as well as neurological conditions such as Parkinson's and Alzheimer's.

"People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep," said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute. "We're actually directly recording neural activity in mice to see what's going on. We are providing a basic circuit to work on in the future to develop different treatments."

Lack of sleep does more than leave you tired. Because growth hormone helps control how the body processes sugar and fat, poor sleep can increase the risk of obesity, diabetes, and heart disease.

The Brain Regions Driving Growth Hormone

The system behind this process is buried deep in the hypothalamus, an ancient part of the brain shared by all mammals. Here, specialized neurons release signals that either trigger or suppress growth hormone.

Two key players are growth hormone releasing hormone (GHRH), which stimulates release, and somatostatin, which inhibits it. Together, they coordinate hormone activity across the sleep-wake cycle.

Once growth hormone enters the system, it activates the locus coeruleus, a brainstem region that controls alertness, attention, and cognitive function. Disruptions in this area are linked to a wide range of neurological and psychiatric disorders.

"Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance," said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. "There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn't been talked about before."

How Sleep Stages Control Hormone Release

To study this system, researchers recorded brain activity in mice by inserting electrodes and stimulating neurons with light. Because mice sleep in short bursts throughout the day and night, they provided a detailed view of how growth hormone changes across sleep stages.

The team found that GHRH and somatostatin behave differently depending on whether the brain is in REM or non-REM sleep.

During REM sleep, both hormones increase, leading to a surge in growth hormone. During non-REM sleep, somatostatin drops while GHRH rises more modestly, still boosting hormone levels but in a different pattern.

A Surprising Feedback Loop in the Brain

The researchers also uncovered a feedback loop that links growth hormone to wakefulness. As sleep continues, growth hormone gradually builds up and stimulates the locus coeruleus, nudging the brain toward waking.

But there is a twist. When this brain region becomes too active, it can actually trigger sleepiness instead, creating a delicate balance between sleep and alertness.

"This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness," Silverman said. "Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health."

Why It Matters for Brain and Body

This balance does more than affect physical growth. Because growth hormone works through brain systems that control alertness, it may also influence how clearly you think and how focused you feel.

"Growth hormone not only helps you build your muscle and bones and reduce your fat tissue, but may also have cognitive benefits, promoting your overall arousal level when you wake up," Ding said.

Funding and Research Team

The research was supported by the Howard Hughes Medical Institute (HHMI) and the Pivotal Life Sciences Chancellor's Chair fund. Yang Dan holds the Pivotal Life Sciences Chancellor's Chair in Neuroscience. The study also included collaborators from UC Berkeley and Stanford University.

Source: ScienceDaily

One fat helped pancreatic cancer grow while another cut disease in half

 For years, the common assumption has been simple: eating less fat may help lower cancer risk. New research suggests the picture is much more complicated.

Scientists report that when it comes to pancreatic cancer, the specific type of fat in the diet may be more important than the total amount consumed.

The findings, published in Cancer Discovery, a journal of the American Association for Cancer Research, indicate that different fats can have dramatically different effects on cancer development.

"It's really the type of fat that you're consuming, not just total fat content," says Christian Felipe Ruiz, PhD, an associate research scientist in Yale School of Medicine's Department of Genetics and lead author of the study. "Depending on the type of fat that you consume, it can go completely different ways. We found that some fats promote cancer, as we would expect, while other fats are really good at suppressing cancer."

Oleic Acid Linked to Faster Tumor Growth

One of the study's most unexpected findings involved oleic acid, the primary fatty acid found in olive oil.

Researchers found evidence that oleic acid may encourage tumor growth in pancreatic cancer, a result that surprised the team because of the fatty acid's long-standing reputation as a heart-healthy dietary fat.

"It's traditionally been considered a healthy type of fat for cardiovascular health," Ruiz says.

The cancer examined in the study was pancreatic ductal adenocarcinoma (PDAC), the most common form of pancreatic cancer and one of the deadliest cancers overall. Only about 13% of people diagnosed with PDAC survive for five years.

"More than 65,000 people are expected to be diagnosed with PDAC in the U.S. this year, with over 50,000 deaths," Ruiz notes. "At the moment, effective treatment options are limited, especially for advanced disease. Therefore, prevention strategies are sorely needed to move the needle on PDAC mortality."

Although previous research has linked high-fat diets to a greater risk of PDAC, scientists have struggled to identify exactly how dietary fat influences the disease. The new study, led by senior author Mandar Deepak Muzumdar, MD, associate professor of genetics and of internal medicine at YSM, sought to answer that question.

Muzumdar is also a member of Yale Cancer Center and the Yale Cancer Biology Institute at West Campus.

Comparing Different Types of Dietary Fat

To isolate the effects of specific fats, the researchers created 12 different high-fat diets. Each diet contained the same number of calories, with the only difference being the source of fat. The diets were designed to reflect common patterns of fat consumption in the modern American diet.

According to Ruiz, many earlier studies relied on a simpler approach.

For decades, researchers commonly "gave mice very high levels of fat in their diet, often using a single fat source." In many cases, those diets derived 60% of calories from lard, which does not accurately reflect typical human eating habits and makes it difficult to determine the effects of individual fatty acids.

"Exactly what components of dietary fat cause cancer has remained a mystery," Ruiz adds.

The results were striking. Mice carrying a genetic mutation that produces a disease closely resembling human PDAC developed tumors more rapidly when fed diets rich in oleic acid. Oleic acid is a monounsaturated fatty acid (MUFA) found in foods such as olive oil, high-oleic safflower oil, high-oleic sunflower oil, peanuts, and lard.

In contrast, diets rich in polyunsaturated fatty acids (PUFAs) slowed cancer development. The strongest protective effects were seen with omega-3 fatty acids, including those found in fish oil.

"When we fed mice diets enriched with fish oil, we saw a 50% reduction in disease compared with mice fed a standard fat diet."

How Dietary Fats Affect Cancer Cell Survival

The findings led researchers to investigate ferroptosis, a form of programmed cell death caused by lipid oxidation.

When fatty acids become part of pancreatic cell membranes, their chemical characteristics influence how easily those cells can be damaged by oxidation. PUFAs are more prone to oxidation, making cancer cells more vulnerable to ferroptosis and death. MUFAs are more resistant to oxidation, helping protect cancer cells from this process.

"Monounsaturated fats really protect the cancer cells from lipid oxidation," Ruiz explains. "Because oxidation is reduced, they're less likely to undergo ferroptosis."

The researchers observed a direct relationship between fat composition and disease severity.

"When we increased the ratio of MUFAs to PUFAs in the diet, disease burden increased. Conversely, when we decreased the ratio, disease burden was reduced."

Source: ScienceDaily

Scientists finally crack an “undruggable” pancreatic cancer target and nearly double survival

 For a long time, the likelihood of surviving pancreatic cancer has been extremely low. For patients who were diagnosed with metastatic pancreatic cancer between 2015 and 2021, about 97% died within five years of their diagnosis.

Pancreatic cancer is so deadly in part because there are no effective screening tests, and it rarely causes noticeable symptoms in its earliest stages. By the time a patient experiences signs, such as jaundice – a yellowing of the skin – or abdominal pain, the cancer has often already spread to other organs.

As a gastrointestinal oncologist and researcher specializing in early-phase clinical trials, I have seen the critical need for more effective therapies for patients with pancreatic cancer. For decades, successfully targeting the central mechanism that causes the vast majority of pancreatic cancers was considered impossible.

However, that narrative is rapidly changing with a new drug that can shut down the key protein that drives pancreatic cancer, nearly doubling survival rates for patients with advanced stages of the disease.

‘Undruggable’ tumors

The standard treatment for advanced pancreatic cancer has historically relied on chemotherapy, potent drugs designed to kill rapidly dividing cells. While chemotherapy can slow the progression of the disease, its effectiveness is often limited by the ability of pancreatic cancer cells to develop resistance against these drugs.

Pancreatic cancer’s success lies in its genetics. More than 90% of pancreatic tumors are driven by mutations in a gene called KRAS. This gene codes for proteins that function as switches that turn cell growth on and off. When the KRAS gene is mutated, the switch becomes permanently stuck in the “on” position, commanding cancer cells to multiply endlessly.

For decades, scientists considered KRAS to be “undruggable.” The surface of the protein is exceptionally smooth, lacking the molecular pockets that standard drugs require to bind to and turn the switch off.

Because existing drugs haven’t been able to target this protein, treatment for pancreatic cancer has primarily relied on toxic drugs that act more like blunt instruments than precise tools. Chemotherapy attempts to control the disease through widespread cell destruction, causing significant collateral damage to healthy tissues that lead to side effects.

What is daraxonrasib?

A new drug called daraxonrasib offers a critical advance in treating metastatic pancreatic cancer.

Daraxonrasib is taken daily by mouth. Instead of binding to KRAS directly, it attaches to a molecule called cyclophilin A in cells that helps fold proteins into their final 3D structures. This protein complex is then able to bind to the active KRAS protein and shut down its ability to signal cancer cells to multiply.

The company developing the drug, Revolution Medicines, presented results on May 31, 2026, from its Phase 3 clinical trial of 500 patients with metastatic pancreatic cancer who had received prior treatment. Compared to standard chemotherapy, daraxonrasib nearly doubled overall survival from 6.7 months to 13.2 months after diagnosis. Overall, daraxonrasib reduced the risk of death for metastatic pancreatic cancer patients by 60%.

The most common side effect is a prominent skin rash, which affected more than 86% of patients in the study. Patients also frequently dealt with stomatitis – painful swelling and sores inside the mouth – as well as diarrhea, nausea and vomiting. However, patients taking daraxonrasib were far less likely to stop treatment due to severe side effects compared to chemotherapy, and they had improved quality of life with reduced pain.

Next steps for daraxonrasib

By successfully targeting the specific genetic mutation that drives the vast majority of pancreatic cancers, researchers have demonstrated that this “undruggable” disease is treatable with targeted therapy.

Source: ScienceDaily

Scientists discover the deep sleep circuit that builds muscle, burns fat, and boosts the brain

 A good night's sleep does far more than leave you feeling refreshed. It also triggers the release of growth hormone, a key hormone that helps build muscle and bone, burn fat, and support healthy growth. That's why athletes value quality sleep for recovery, and why teenagers need enough sleep to reach their full height potential.

Scientists have long known that growth hormone levels rise during sleep, especially during the deep, non-REM stage. What has remained unclear is exactly how the brain controls this process.

Now, researchers at the University of California, Berkeley have uncovered the brain circuitry responsible for regulating growth hormone during sleep. Their study, published in the journal Cell, also reveals a previously unknown feedback system that helps keep growth hormone levels in balance.

The discovery offers new insight into the close relationship between sleep and hormone regulation. It could eventually guide new treatments for sleep disorders linked to metabolic diseases such as diabetes, as well as neurodegenerative conditions including Parkinson's and Alzheimer's disease.

"People know that growth hormone release is tightly related to sleep, but only through drawing blood and checking growth hormone levels during sleep," said study first author Xinlu Ding, a postdoctoral fellow in UC Berkeley's Department of Neuroscience and the Helen Wills Neuroscience Institute. "We're actually directly recording neural activity in mice to see what's going on. We are providing a basic circuit to work on in the future to develop different treatments."

Because growth hormone also helps regulate glucose and fat metabolism, consistently poor sleep may increase the risk of obesity, diabetes, and cardiovascular disease.

How the Brain Controls Growth Hormone During Sleep

The nerve cells that coordinate growth hormone release are located deep within the hypothalamus, an ancient brain region found across mammals. These include growth hormone-releasing hormone (GHRH) neurons, along with two different types of somatostatin neurons.

Once growth hormone is released, it activates neurons in the locus coeruleus, a brainstem region involved in alertness, attention, thinking, and responding to new experiences. Problems affecting the locus coeruleus have been linked to numerous neurological and psychiatric disorders.

"Understanding the neural circuit for growth hormone release could eventually point toward new hormonal therapies to improve sleep quality or restore normal growth hormone balance," said Daniel Silverman, a UC Berkeley postdoctoral fellow and study co-author. "There are some experimental gene therapies where you target a specific cell type. This circuit could be a novel handle to try to dial back the excitability of the locus coeruleus, which hasn't been talked about before."

Mapping the Sleep Growth Hormone Circuit

Working in the laboratory of Yang Dan, professor of neuroscience and molecular and cell biology at UC Berkeley, the research team studied the brain circuits in mice by placing electrodes in their brains and stimulating hypothalamic neurons with light while recording neural activity.

Mice naturally sleep in short bursts lasting only a few minutes throughout the day and night. That pattern allowed researchers to repeatedly observe changes in growth hormone activity across many sleep and wake cycles.

Using advanced circuit tracing techniques, the team discovered that the two peptide hormones responsible for regulating growth hormone release behave differently depending on the stage of sleep. GHRH promotes growth hormone release, while somatostatin suppresses it.

During REM sleep, both GHRH and somatostatin increase, leading to greater growth hormone release. During non-REM sleep, however, somatostatin levels fall while GHRH rises only moderately, creating a different pattern of hormone regulation.

A Feedback Loop That Balances Sleep and Wakefulness

The researchers also identified a previously unknown feedback mechanism involving the locus coeruleus.

As growth hormone gradually builds up during sleep, it stimulates the locus coeruleus and encourages wakefulness. But if activity in the locus coeruleus becomes too high, it unexpectedly begins promoting sleepiness instead, a finding Silverman reported earlier this year.

"This suggests that sleep and growth hormone form a tightly balanced system: Too little sleep reduces growth hormone release, and too much growth hormone can in turn push the brain toward wakefulness," Silverman said. "Sleep drives growth hormone release, and growth hormone feeds back to regulate wakefulness, and this balance is essential for growth, repair and metabolic health."

Because growth hormone influences the locus coeruleus, which plays a central role in maintaining alertness during the day, this newly identified system may also affect attention and other aspects of cognitive function.

Source: ScienceDaily