New research suggests that disrupted brain circuits in Down syndrome may be linked to a shortage of a specific molecule that the nervous system relies on to develop and work properly. The team says that bringing this molecule back, known as pleiotrophin, might help support brain function in Down syndrome and potentially other neurological conditions, possibly even later in life.
The work was done in laboratory mice, not in people, so it is not close to becoming a treatment. Even so, the researchers found that giving pleiotrophin improved brain function in adult mice after the brain had already finished forming. This raises the possibility of an advantage over earlier strategies aimed at strengthening Down syndrome related brain circuits, which would have required action during very narrow windows in pregnancy.
"This study is really exciting because it serves as proof-of-concept that we can target astrocytes, a cell type in the brain specialized for secreting synapse-modulating molecules, to rewire the brain circuitry at adult ages," said researcher Ashley N. Brandebura, PhD, who was part of the research team while at the Salk Institute for Biological Studies and is now part of the University of Virginia School of Medicine. "This is still far off from use in humans, but it gives us hope that secreted molecules can be delivered with effective gene therapies or potentially protein infusions to improve quality of life in Down syndrome."
Understanding Down syndrome and its health impacts
Down syndrome affects about 1 in 640 babies born each year in the United States, according to the federal Centers for Disease Control and Prevention. It results from an error in cell division during development and can be associated with developmental delays, hyperactivity, a shorter lifespan, and a higher risk of health issues that can include heart defects, thyroid problems, and hearing or vision difficulties.
Salk scientists led by Nicola J. Allen, PhD, set out to learn more about what drives Down syndrome by examining proteins inside brain cells in mouse models of the condition. They focused on pleiotrophin because it normally appears at very high levels at key stages of brain development and plays important roles in building synapses, the connections between nerve cells, and in shaping axons and dendrites, which help neurons send and receive signals. The researchers also noted that pleiotrophin levels are reduced in Down syndrome.
To test whether restoring pleiotrophin could improve brain function, the team used engineered viruses called viral vectors to deliver it to the right place. Viruses are often associated with illnesses like the flu, but researchers can modify them so they do not cause disease and instead carry helpful material. In this case, the virus was stripped of harmful components and loaded with beneficial cargo -- pleiotrophin -- so it could deliver the molecule directly into cells.
Astrocytes, synapses, and brain plasticity
The scientists reported that supplying pleiotrophin to astrocytes, a major type of brain cell, produced substantial effects. Among the changes, the number of synapses increased in the hippocampus, a region involved in learning and memory. The team also saw an increase in brain "plasticity" -- the ability to create or adjust connections that support learning and memory.
"These results suggest we can use astrocytes as vectors to deliver plasticity-inducing molecules to the brain," Allen said. "This could one day allow us to rewire faulty connections and improve brain performance."
Broader implications and next steps
The researchers emphasize that pleiotrophin is unlikely to be the only factor behind circuit problems in Down syndrome. They say more work is needed to understand the many contributors involved. Still, they argue that the results show the approach itself can work, and that it might eventually help beyond Down syndrome, including in other neurological diseases.
"This idea that astrocytes can deliver molecules to induce brain plasticity has implications for many neurological disorders, including other neurodevelopmental disorders like fragile X syndrome but also maybe even to neurodegenerative disorders like Alzheimer's disease," Brandebura said. "If we can figure out how to 'reprogram' disordered astrocytes to deliver synaptogenic molecules, we can have some greatly beneficial impact on many different disease states."
After finishing her postdoctoral training at Salk, Brandebura plans to continue this line of research at UVA Health. There, she is part of the UVA Brain Institute, the Department of Neuroscience and the Center for Brain Immunology and Glia (BIG Center).
Findings published and funding
The results were published in the journal Cell Reports. The article is opening access, meaning it is free to read. The research team included Brandebura, Adrien Paumier, Quinn N. Asbell, Tao Tao, Mariel Kristine B. Micael, Sherlyn Sanchez and Allen. The scientists report no financial interest in the work.
Support came from the Chan Zuckerberg Initiative and the National Institutes of Health's National Institute of Neurological Disorders and Stroke, grant F32NS117776.
Growing seasonal concern about overlapping respiratory illnesses such as the common cold and influenza has increased interest in ways to support immune health. New clinical research now suggests that kimchi, a traditional Korean fermented food, can help strengthen immune cell function while keeping the immune system in balance.
Scientists have found that regular kimchi consumption supports the body's ability to defend against threats without triggering unnecessary immune activity. The findings add scientific weight to kimchi's long-held reputation as a health-promoting food.
Single Cell Study Reveals How Kimchi Regulates Immunity
The World Institute of Kimchi (President: Hae Choon Chang), a government-funded research organization under the Ministry of Science and ICT, released results from an advanced single-cell genetic study examining kimchi's effects on human immunity. The analysis indicates that kimchi has immunomodulatory properties, meaning it can calm excessive immune reactions while also improving protective immune functions.
According to the researchers, this is the first study worldwide to identify kimchi's immune-related effects at the single-cell level. The results also suggest that kimchi may benefit not only metabolic health but immune health as well.
Human Trial Design and Advanced Genetic Analysis
The clinical trial involved overweight adults who were divided into three groups (n = 13 each). Over a 12-week period, participants consumed either a placebo, kimchi powder made from naturally fermented kimchi, or kimchi powder produced using a starter culture fermentation method.
At the end of the intervention, researchers collected peripheral blood mononuclear cells (PBMCs) and analyzed them using single-cell transcriptomics analysis (scRNA-seq). This technique allowed the team to monitor changes in gene activity within individual immune cells, revealing subtle immune shifts that traditional testing methods often fail to detect.
Immune Cells Show Stronger Defense and Better Balance
The findings showed that participants who consumed kimchi experienced enhanced activity in antigen-presenting cells (APCs), which play a key role in detecting bacteria and viruses and signaling other immune cells. The study also found that CD4+ T cells developed into both protective and regulatory types in a balanced way.
These outcomes suggest that kimchi does more than simply activate immune responses. Instead, it functions as a "precision regulator," boosting immune defenses when needed while preventing excessive or unnecessary immune reactions.
Fermentation Method Influences Immune Benefits
Researchers also observed differences based on how the kimchi was fermented. While both naturally fermented kimchi and starter-fermented kimchi supported immune balance, the starter-fermented version produced stronger effects. These included improved antigen recognition by immune cells and a greater reduction in unnecessary immune signaling.
The team noted that these findings point to the potential for enhancing kimchi's health benefits through controlled fermentation technologies in the future.
Dr. Woo Jae Lee of the World Institute of Kimchi, who led the research, said, "Our research has proven for the first time in the world that kimchi has two different simultaneous effects: activating defense cells and suppressing excessive response." He added, "We plan to expand international research on kimchi and lactic acid bacteria in relation to immune and metabolic health in the future."
Kimchi's Growing Role as a Functional Food
The study helps position kimchi not only as a traditional fermented dish but as a functional food with scientifically demonstrated immune benefits. Researchers expect the findings to support future applications ranging from the development of health functional foods to improving vaccine effectiveness and reducing the risk of immune-related diseases.
The research was published in npj Science of Food (IF 7.8), a leading international journal in the field of food science.
Why do some children develop a brain that is unusually small (microcephaly)? A global team of scientists from the German Primate Center -- Leibniz Institute for Primate Research (DPZ), Hannover Medical School (MHH), and the Max Planck Institute of Molecular Cell Biology and Genetics set out to answer this question using human brain organoids. These lab-grown models allowed the researchers to closely examine how changes in key structural proteins inside cells can interfere with early brain development.
Their work, documented in EMBO Reports, shows that mutations in actin genes disrupt how early brain progenitor cells divide. When these cells fail to divide correctly, their numbers drop, limiting overall brain growth and resulting in a smaller brain. "Our findings provide the first cellular explanation for microcephaly in people with the rare Baraitser-Winter syndrome," says Indra Niehaus, first author of the study and research associate at Hannover Medical School.
How the Cell's Internal Framework Shapes Brain Development
Actin plays a central role in the cytoskeleton, the internal framework that gives cells structure and helps move materials inside them. In people with Baraitser-Winter syndrome, a mutation affects one of two crucial actin genes. To understand the consequences, the researchers reprogrammed skin cells from affected patients into induced pluripotent stem cells. These stem cells were then used to grow three-dimensional brain organoids that mimic early stages of human brain formation.
After thirty days of development, the differences were striking. Organoids grown from patient cells were about 25 percent smaller than those grown from healthy donor cells. The ventricle-like regions inside the organoids, where progenitor cells gather and begin forming early nerve cells, were also much smaller.
A Shift in Crucial Brain Cell Populations
When the scientists examined the types of cells inside the organoids, they found a clear imbalance. The number of apical progenitor cells, which are essential for building the cerebral cortex, was significantly lower. At the same time, there was an increase in basal progenitor cells, which usually appear later as development progresses.
This shift suggested that the timing and outcome of cell division had been altered, potentially explaining why the brain tissue failed to expand normally.
When Cell Division Orientation Goes Wrong
Using high-resolution microscopy, the team closely tracked how apical progenitor cells divided. Under normal conditions, these cells divide mainly at right angles to the ventricular surface. This orientation ensures that cellular components are evenly shared and that two new apical progenitor cells are produced.
In organoids carrying the actin mutation, this pattern changed dramatically. Vertical divisions became far less common, while horizontal and angled divisions dominated. As a result, apical progenitor cells were less able to renew themselves. They detached from the ventricular zone more often and were more likely to become basal progenitor cells instead.
"Our analyses show very clearly that a change in the division orientation of the progenitor cells is the decisive trigger for the reduced brain size," says Michael Heide, group leader at the German Primate Center and last author of the study. "A single change in the cytoskeleton is sufficient to disrupt the course of early brain development."
Tiny Structural Changes With Lasting Effects
Electron microscopy revealed additional, subtle defects at the ventricular surface. Cell shapes appeared uneven, and extra protrusions formed between neighboring cells. Researchers also observed unusually high levels of tubulin at cell junctions. Tubulin is another cytoskeletal protein that plays a key role in cell division.
Although the overall structure of the cells remained intact, these small abnormalities may be enough to permanently alter how cells orient themselves during division.
Proving the Mutation Is the Cause
To confirm that the observed differences were truly caused by the actin mutation and not by other genetic variations, the researchers performed a crucial control experiment. They used CRISPR/Cas9 to introduce the exact same mutation into a healthy stem cell line. Brain organoids grown from these edited cells developed the same defects seen in patient-derived organoids -- a proof that the mutation itself is the driving factor.
What This Discovery Means for Medicine
The findings shed light on how rare genetic mutations can lead to complex brain malformations and demonstrate the value of brain organoids in biomedical research. "Our findings help us understand how rare genetic disorders lead to complex brain malformations and highlight the potential of brain organoids for biomedical research," says Michael Heide.
"The therapeutic potential of this study lies in diagnostics, as our data helps to better classify genetic findings in patients. Since the disease affects early fetal development processes, interventions in humans would be complex. However, new drugs that influence the interaction between actin and microtubules could open up new approaches in the long term," says Nataliya Di Donato, Director of the Institute of Human Genetics at Hannover Medical School.
Even when Americans have health insurance, they can have a hard time affording the drugs they’ve been prescribed[1].
About 1 in 5 U.S. adults skip filling a prescription due to its cost at least once a year, according to KFF[2], a health research organization. And 1 in 3 take steps to cut their prescription drug costs, such as splitting pills when it’s not medically necessary or switching to an over-the-counter drug...