Research advances from the National Institutes of Health (NIH) Intramural Research Program (IRP) often make headlines. Read the news releases that describe our most recent findings:
Whether you’re shedding pounds with the help of effective new medicines, slimming down after weight loss surgery or cutting calories and adding exercise, there will come a day when the numbers on the scale stop going down, and you hit the dreaded weight loss plateau.
In a recent study, Kevin Hall, a researcher at the National Institutes of Health who specializes in measuring metabolism and weight change, looked at when weight loss typically stops depending on the method people were using todrop pounds. He broke down the plateau into mathematical models using data from high-quality clinical trials of different ways to lose weight to understand why people stop losing when they do. The study published Monday in the journal Obesity.
A new study led by scientists in the Center for Cancer Research (CCR) at the National Cancer Institute (NCI) sheds light on one way tumors may continue to grow despite the presence of cancer-killing immune cells. The findings, published March 29, 2019, in Science, suggest a way to enhance the effectiveness of immunotherapies for cancer treatment. NCI is part of the National Institutes of Health.
Dying cancer cells release the chemical potassium, which can reach high levels in some tumors. The research team reported that elevated potassium causes T cells to maintain a stem-cell-like quality, or “stemness,” that is closely tied to their ability to eliminate cancer during immunotherapy. The findings suggest that increasing T cells’ exposure to potassium — or mimicking the effects of high potassium — could make cancer immunotherapies more effective.
“This study helps us better understand why cancer immunotherapy works the way it does,” said Nicholas Restifo, M.D., of NCI’s CCR, who led the research team. “It could also point the way toward generating better and more long-lasting responses to these treatments.”
National Institutes of Health scientists studying the progression of inherited and infectious eye diseases that can cause blindness have found that microglia, a type of nervous system cell suspected to cause retinal damage, surprisingly had no damaging role during prion disease in mice. In contrast, the study findings indicated that microglia might delay disease progression.
The discovery could apply to studies of inherited photoreceptor degeneration diseases in people, known as retinitis pigmentosa. In retinitis pigmentosa cases, scientists find an influx of microglia near the photoreceptors, which led to the belief that microglia contribute to retina damage.
These inherited diseases appear to damage the retina similarly to prion diseases. Prion diseases are slow degenerative diseases of the central nervous system that occur in people and various other mammals. No vaccines or treatments are available, and the diseases are almost always fatal. Prion diseases primarily involve the brain but also can affect the retina and other tissues.
Microglia have been shown to be beneficial in slowing prion disease progression in the brain, and now in retina. Microglial cells (green) are engulfing and eliminating prion-damaged photoreceptors (red), which appears to slow retinal degeneration.
Technique could aid early detection and treatment of certain eye diseases
Cells of the retinal pigment epithelium (RPE) form unique patterns that can be used to track changes in this important layer of tissue in the back of the eye, researchers at the National Eye Institute (NEI) have found. Using a combination of adaptive optics imaging and a fluorescent dye, the researchers used the RPE patterns to track individual cells in healthy volunteers and people with retinal disease. The new finding could provide a way to study the progression and treatment of blinding diseases that affect the RPE. The study was published today in the journal JCI Insight. NEI is part of the National Institutes of Health (NIH).
“Studying cells of the retinal pigment epithelium in the clinic is like looking into a black box. RPE cells are difficult to see, and by the time signs of disease are detectable with conventional techniques, a lot of damage has often already occurred,” said Johnny Tam, Ph.D., the lead author of the study. “This study is proof-of-concept that we can use a fluorescent dye to reveal this unique fingerprint of the RPE, and to monitor the tissue over time.”
People taking the mineral for other medical reasons should stay the course
Eating a calcium-rich diet or taking calcium supplements does not appear to increase the risk of age-related macular degeneration (AMD), according to the findings of a study by scientists at the National Eye Institute (NEI). AMD is a leading cause of vision loss and blindness among people age 65 and older in the United States. The study findings are published in JAMA Ophthalmology.
The findings contradict an earlier study indicating that high levels of calcium were associated with increased prevalence of AMD, but they are consistent with another suggesting that calcium has a protective role in AMD.
“Although the findings suggest that high calcium intake may be protective, the jury is still out on whether people should alter their calcium intake to prevent the onset or progression of AMD,” said the study’s lead investigator, Emily Chew, M.D., director of the Division of Epidemiology and Clinical Applications and the deputy clinical director at NEI, which is part of the National Institutes of Health.
Calcium-rich foods include milk, yogurt and cheese, as well as non-dairy sources such as kale, white beans and sesame seeds.
Approximately 1 in 9 women in the United States experiences symptoms of postpartum depression, according to the Centers for Disease Control and Prevention. Now, the U. S. Food and Drug Administration (FDA) has approved brexanolone, an analog of the endogenous human hormone allopregnanolone and the first drug specifically designed to treat postpartum depression.
Some psychiatric drugs owe their discovery to chance — serendipitous observations of clinical benefit — or a process of incremental improvement based on drugs previously discovered by chance. Not so with brexanolone, which has a truly novel mechanism of action and was developed by design, thanks to a series of basic and translational neuroscience studies. FDA approval represents the final phase of a bench-to-bedside journey for this drug — a journey that began in the NIMH Intramural Research Program (IRP).
In the 1980s, NIMH IRP researchers discovered that metabolites (products formed when the body breaks down or “metabolizes” other substances) of the steroid hormones progesterone and deoxycorticosterone bound to and acted upon receptors for gamma-aminobutyric acid (GABA) — a major inhibitory neurotransmitter in the brain. These steroids were found to amplify GABA-activated chloride ion currents, thereby impacting the excitability of neurons.
NIH study finds new cell composition may lead to less effective future response
Meningitis, a group of serious diseases which infect the brain’s lining, leaves its mark and can affect the body’s ability to fight such infections in the future. According to a new study published in Nature Immunology, infections can have long-lasting effects on a population of meningeal immune cells, replacing them with cells from outside the meninges that then change and become less likely to recognize and ward off future attacks. The research was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“After an infection, the immune cell landscape in the brain lining changes. Brain lining immune cells that normally protect the brain from foreign invaders die and are replaced by cells from elsewhere in the body. These new cells are altered in a way that affects how they respond to subsequent challenges and new infections,” said Dorian McGavern, Ph.D., NINDS scientist and senior author of the study.
Using real time imaging, Dr. McGavern and his colleagues took a detailed look at mouse meningeal macrophages, which are immune cells that live in the meninges, the protective layers covering the brain and spinal cord. One group of these macrophages is found along blood vessels in the dura mater (the outermost layer of the meninges) and helps catch pathogens from the blood before they reach brain tissue. Blood vessels in the dura mater are relatively open compared to the tightly sealed vessels found in other brain regions, and macrophages in the dura mater often serve as the first line of defense against harmful blood-borne agents.
Meningeal macrophages (shown in white, red, and blue) are on constant alert against potential threats to brain tissue.
Using fMRI, researchers uncover the neural underpinnings, which could aid development of potential treatments
Researchers have identified changes in brain connectivity and brain activity during rest and reward anticipation in children with anhedonia, a condition where people lose interest and pleasure in activities they used to enjoy. The study, by scientists at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, sheds light on brain function associated with anhedonia and helps differentiate anhedonia from other related aspects of psychopathology. The findings appear in the journal JAMA Psychiatry.
Anhedonia is a risk factor for, and a symptom of, certain mental disorders and is predictive of illness severity, resistance to treatment, and suicide risk. While researchers have sought to understand the brain mechanisms that contribute to anhedonia, investigations on this condition have more commonly focused on adults rather than children. Importantly, previous studies often did not separate anhedonia from other related psychopathologies, such as low mood, anxiety, or attention-deficit/hyperactivity disorder.
“Understanding the neural mechanisms of anhedonia that are distinguishable from other psychiatric concerns is important for clinicians to develop on-target treatments,” said lead study author Narun Pornpattananangkul, Ph.D., a postdoctoral fellow in the Emotion and Development Branch, part of NIMH’s Division of Intramural Research Programs. “Yet, disentangling shared characteristics from unique neural mechanisms of anhedonia is challenging because it often co-occurs with other psychiatric conditions.”
Image showing differences in fMRI activation between children with and without anhedonia during reward-anticipation.
These exceptional early stage scientists continue agency commitment to the next generation of biomedical researchers
The National Institutes of Health has selected eight scientists as Lasker Clinical Research Scholars, part of a joint initiative with the Albert and Mary Lasker Foundation, to foster the next generation of great clinical scientists. This highly competitive program provides talented, early stage researchers the opportunity to carry out independent clinical and translational research for five to seven years at NIH. The researchers also have the possibility of additional years of financial support, at NIH or an NIH-funded research institution, upon project review. The new researchers join 15 Lasker Scholars hired since 2012.
“Adding to the impressive cadre of Lasker Scholars at NIH, these new clinician-scientists will continue to produce innovative discoveries that affirm our investment in some of the boldest young minds in biomedical research,” said NIH Director Francis S. Collins, M.D., Ph.D.
Lasker Scholars have access to the NIH Clinical Center, the largest hospital in the world devoted to clinical research. The Lasker Foundation will provide additional developmental support to the scholars while they are working at NIH by funding travel to scientific meetings and providing the opportunity to participate in selected foundation activities, including the Lasker Award ceremonies.
Findings highlight the importance of screening kids as young as 10 for suicide risk in emergency settings
A research team found nearly one-third of youth ages 10 to 12 years screened positive for suicide risk in emergency department settings. As part of a larger study on youth suicide risk screening in emergency departments, researchers at the National Institute of Mental Health (NIMH), part of the National Institutes of Health, and collaborators sought to explore how frequently preteen youth ages 10 to 12 screened positive for suicide risk. Notably, seven percent of the preteens who screened positive for suicide risk were seeking help for physical – not psychiatric – concerns. The study appears online March 11 in Hospital Pediatrics.
“Typically, suicidal thoughts and behaviors are seen in older teens. It was troubling to see that so many preteens screened positive for suicide risk, and we were alarmed to find that many of them had acted on their suicidal thoughts in the past,” said Lisa Horowitz, Ph.D., M.P.H., a clinical scientist in the NIMH Division of Intramural Research Programs (DIRP) and an author on the paper. “This study shows that children as young as 10 who show up in the emergency department may be thinking about suicide, and that screening all preteens — regardless of their presenting symptoms — may save lives. Otherwise, they may pass through our medical systems undetected.”
Assessing the patterns of energy use and neuronal activity simultaneously in the human brain improves our understanding of how alcohol affects the brain, according to new research by scientists at the National Institutes of Health. The new approach for characterizing brain energetic patterns could also be useful for studying other neuropsychiatric diseases. A report of the findings is now online in Nature Communications.
“The brain uses a lot of energy compared to other body organs, and the association between brain activity and energy utilization is an important marker of brain health,” said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of NIH, which funded the study. “This study introduces a new way of characterizing how brain activity is related to its consumption of glucose, which could be very useful in understanding how the brain uses energy in health and disease.”
The research was led by Dr. Ehsan Shokri-Kojori and Dr. Nora D. Volkow of the NIAAA Laboratory of Neuroimaging. Dr. Volkow is also the director of the National Institute on Drug Abuse at NIH. In previous studies they and their colleagues have shown that alcohol significantly affects brain glucose metabolism, a measure of energy use, as well as regional brain activity, which is assessed through changes in blood oxygenation.
“The findings from this study highlight the relevance of energetics for ensuring normal brain function and reveal how it is disrupted by excessive alcohol consumption,” says Dr. Volkow.
NIH scientists present a new method for combining measures of brain activity (left) and glucose consumption (right) to study regional specialization and to better understand the effects of alcohol on the human brain.
