Day: September 5, 2025

Categories : Mental Health Obstetrics & GynaecologyTags : Leave a comment

Placenta Acts to Shield Foetus from Serotonin

On By ModernMedia
Image by Scientific Animations CC4.0

The placenta has long been thought to produce serotonin during pregnancy. But in a new study, Yale researchers shatter the deep-rooted hypothesis – and show that the placenta doesn’t produce serotonin but instead regulates its delivery to the embryo and foetus. They found that serotonin comes from the pregnant parent, with the placenta acting as a “serotonin shield” that controls how much reaches the embryo and foetus. 

The findings, published in the journal Endocrinology, could offer critical insights into how a parent’s serotonin levels might affect the development of their baby’s body and brain, the researchers say. 

“The placenta is in essence the ‘serotonin shield’ that regulates how much serotonin is ultimately delivered to the embryo and foetus, not the source of serotonin,” said Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine and corresponding author of the study. “Why does this matter? Because now we correctly know where this delivery is regulated.”

Often called a “happiness hormone,” serotonin regulates mood, so it’s often associated with the brain. In reality, less than 5% of serotonin is made in the brain, with 95% of it made in the gut. But serotonin does more than just regulate mood. It’s also a growth hormone. In the gut, it gets taken up by platelets and is delivered to parts of the body that need to grow, including in wound healing. 

During pregnancy, serotonin also helps with growth: It travels into the placenta through a special protein known as the serotonin transporter (SERT) where it plays a critical role in the development of the embryo and foetus. 

Serotonin from the mother is taken up by the foetal placenta, which then produces a myriad of hormones, growth factors, and regulators that are delivered to the foetus.

For the new study, researchers sought to better understand these relationships by using a pure source of placenta cells, unlike in previous studies that looked at either whole animals or isolated mouse placentas. To do so, they first purified human cytotrophoblasts, which are the stem cells that make all the cells of the placenta. They then added serotonin to those cells to see where it would go and discovered it concentrated in the nucleus. Next, they used a selective serotonin reuptake inhibitor (SSRI) that blocked SERT, escitalopram, to show that the normal growth, function, and differentiation of these cells was completely blocked. 

They also used another inhibitor called cystamine to block serotonylation, or the process by which serotonin is added to proteins like histone 3, which turns genes “on” and “off.” Again, that completely blocked the normal growth of the cells. 

Blocking either SERT or serotonylation led to significant changes in gene expression of RNAs in the cytotrophoblasts, they found. Some genes, including ones involved in making, moving, and growing cells, became downregulated, or less active, when serotonin couldn’t enter the cell. Other gene, including ones that help cells stay alive and protect them, became upregulated, or more active. According to the researchers, these findings show that serotonin is critical for the growth of the cytotrophoblasts, the placenta, and by extension, the foetus. 

Additionally, researchers discovered that the cytotrophoblasts don’t contain tryptophan hydroxylase (TPH-1), or the enzyme that makes serotonin, indicating the cells within the placenta can’t produce serotonin on their own. 

“This suggests that factors that either inhibit serotonin transport through the placenta, or increase it, may have a significant impact on the placenta, embryo, foetus, and ultimately, the newborn and its brain,” Kliman said.

For example, Kliman says this explains why taking SSRIs, which decrease the levels of serotonin into the placenta, leads to smaller babies, and why, conversely, increased levels of serotonin may lead to bigger babies, with bigger brains, who may be at increased risk for developmental disabilities like autism.

Kliman and his lab have long investigated the link between placentas and children with autism, specifically the number of trophoblast inclusions (TIs) in the placenta. TIs are like wrinkles or folds in the placenta, caused by cells multiplying more than they should, typically only seen in pregnancies where there are genetic problems with the foetus. 

This new study is the culmination of research first published in 2006 that found significantly more TIs in the placentas from children with autism, and later in 2021, that the genetics of the foetus, and not the parent’s uterine environment, determine how many TIs are in the placenta. 

“This puts a big nail into the theory that vaccines cause autism,” suggested Kliman. “Autism, in essence, starts in the womb, not after delivery, and is most likely due to the genetics of the placenta and to a lesser extent, the maternal environment the placenta finds itself in.”

Source: Yale News

Categories : Cancer GastrointestinalTags : Leave a comment

Scientists Find Few Links Between Cancer and Microbiome

On By ModernMedia
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

About a dozen studies in the past five years have made claims linking nearly every type of human cancer with the presence of microbiomes, “communities” of bacteria, viruses and fungi that live in or on peoples’ bodies. Now, scientists at Johns Hopkins Medicine say a study that sequenced human cancers found far less microbial DNA sequences than earlier studies reported in the same cancer tissue samples.

“It’s the nature of science to validate, confirm and reproduce findings,” says Steven Salzberg, PhD, Professor of Biomedical Engineering, Computer Science, and Biostatistics at The Johns Hopkins University. “Over time, we see a more complete picture of new research, and in this case, we did not find any associations between microbiomes and many types of cancer.”

Salzberg says details of the new study, published Sept. 3 in Science Translational Medicine, surveyed the whole genome sequences generated from 5734 tissue samples collected from 25 cancer types and stored in a large National Cancer Institute-funded database, The Cancer Genome Atlas (TCGA). About half of the samples are from normal tissues and blood, the other half from solid tumours and blood-based cancers.

The TCGA’s whole genome sequencing data contains millions of chopped up pieces of DNA molecules, known as reads, from each tissue sample. The original goal of the TCGA studies was to identify mutations in the DNA sequence of genes that might be associated with various cancer types. Sometimes, though, the original tumors might have microbes in them, and the reads could be used to identify those microbes.

Because reads often contain contaminants from bits of DNA left behind in sequencing machinery or picked up from the air or surfaces, samples can acquire DNA from those sources, as well as from the original tumour tissues. Salzberg says extraordinary efforts were made to identify such contaminants, preventing their study from displaying false results.

To rule out contaminants, Salzberg and his team relied on extensive experience with genomic sequencing and careful analysis of control samples to identify reads belonging to sequences known or highly likely to have contaminated samples.  

For the current study, a continuation of one that the Johns Hopkins team published in 2023, Salzberg and first author Yuchen “Peter” Ge, a graduate student in biomedical engineering at Johns Hopkins, removed human DNA sequences from the TCGA data sets by mapping each read against two human reference genomes – one from the Telomere-to-Telomere (T2T) project and another from the Genome Reference Consortium.

After removing human DNA, the research team was left with, on average, 2.4 million reads per sample, or about 0.35% of the total 6.5 billion tumour sample reads. Of these, the research team found 323 million human DNA reads that weren’t eliminated in the first pass and 986 million reads they classified as contaminants.

They next compared the remaining sequencing reads against a database containing 50 651 genomes representing 30,355 species of bacteria, viruses, fungi and archaea (single-celled organisms that aren’t bacteria or viruses).

After removing human DNA sequences and contaminants, the average proportion of microbial DNA reads in solid tumour samples was 0.57% and 0.73% in blood cancers.

The Johns Hopkins researchers then compared their new results to a study published five years ago in the journal Nature [since retracted, because of concerns about contaminants in the microbial data], and found the previous study identified 56 times as many microbial reads as the new study for half of the total microbial reads. And 5% of the time, the previous study found 9,000 times the number of microbial reads as the current Johns Hopkins study. Salzberg says the microbial reads in the retracted study were highly likely to be contaminants.

“This disparity in the number of microbial reads didn’t occur in just a few samples,” says Salzberg. “Over the whole study, the previous researchers found far more microbial reads than we did.”

In another comparison of a study published in Cell in 2022 and the current Johns Hopkins work, the 2022 study reported fungal DNA amounts that were hundreds of times more than what was found in the current Johns Hopkins study, largely due to contaminants.

Among the DNA samples in the current Johns Hopkins study, in which they did find microbiome DNA, the researchers found microbes that have long been linked with human cancer, such as HPV (linked with cervical and some head and neck cancers), Helicobacter pylori (linked to stomach cancer), and Fusobacterium nucleatum and Bacteroides fragilis (linked with GI cancers).

The current Johns Hopkins study and the previous ones published in Cell and Nature reported microbiomes of Saccharomyces cerevisiae, commonly known as baker’s yeast. “It’s one of the most common contaminants in sequencing labs,” says Salzberg. They also found a virus that infects plant fungi, Rosellinia necatrix partitivirus 8, which has no known link to human disease.

Salzberg said the need to carefully document claims about the links between cancer and microbiomes is “especially important” as efforts ramp up to diagnose cancers early using microbiome information.

The Johns Hopkins researchers have made their sequencing analysis data available online to other scientists in the supplementary materials in Science Translational Medicine and online.

Source: Johns Hopkins Medicine

Categories : Neurodegenerative DiseasesTags : Leave a comment

Investigating Why Memory Circuits Break Down in Alzheimer’s Disease

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Scientists are investigating a small region of the brain that plays a major role in memory, spatial navigation, and perhaps Alzheimer’s disease. One of the first parts of the brain affected by Alzheimer’s disease is the entorhinal cortex – a region that plays a big role in memory, spatial navigation, and the brain’s internal mapping system.

With support announced in September from the Commonwealth of Virginia’s Alzheimer’s and Related Diseases Research Award Fund, Virginia Tech scientists Sharon Swanger and Shannon Farris are working to understand why this area is especially vulnerable.

Swanger studies how brain cells communicate across synapses, while Farris focuses on how memory at the molecular level. Their overlapping expertise made the collaboration a natural fit.

“We’ve both been studying for a while,” said Swanger, assistant professor at the Fralin Biomedical Research Institute at VTC. “This new collaborative project brings together my work on synapses and Shannon’s on mitochondria in a way that addresses a big gap in the field.”

“This kind of state-level support is critical,” said Farris, also an assistant professor at the research institute. “It gives researchers in Virginia the chance to ask questions that may eventually make a difference for people living with Alzheimer’s. It’s meaningful to be part of research that could help people facing that journey.”

A key focus of their research is mitochondria – tiny structures inside brain cells that provide the energy needed for a variety of cellular functions in neurons including transmission. In Alzheimer’s disease, mitochondria stop working properly early in the course of the disease.

Farris and Swanger are investigating whether mitochondria in a vulnerable memory-related circuit may become overloaded with calcium, a key signaling chemical for multiple neuronal and synaptic processes. That overload could contribute to the early breakdown of memory.

“The connection between these cells is one of the first to fail in Alzheimer’s,” Farris said. “We found that this synapse has unusually strong calcium signals in nearby mitochondria – so strong we can see them clearly under a light microscope. Those kinds of signals are hard to ignore. It gives us a model where we can really watch what’s happening as things start to go wrong.”

To test their hypothesis, the researchers will study brain tissue from healthy mice and mice with Alzheimer’s. By comparing how mitochondria function and how brain cells communicate across synapses in each group, they hope to find early signs of stress or failure in the entorhinal cortex–hippocampus circuit.

Source: Virginia Tech

Categories : Mental HealthTags : Leave a comment

ADHD Medication Linked to Lower Risk of Suicide Attempts, Substance Abuse, and Criminality

On By ModernMedia
Photo by Inzmam Khan

People who take medication for ADHD have a lower risk of suicide attempts, substance abuse, traffic accidents, and criminality than people with ADHD who do not take medication. This is shown in a new study by researchers from Karolinska Institutet and University of Southampton, published in the journal BMJ.

ADHD, which affects about 5% of children and 2.5% of adults globally, is associated with an increased risk of suicide attempts, substance abuse, accidents, and crime, among other things. 

The researchers behind the study wanted to investigate whether ADHD medication reduces the risk of these outcomes by analysing Swedish national registry data between 2007 and 2020. 

A total of nearly 150 000 individuals between the ages of 6 and 64 with newly diagnosed ADHD were included. The average age in the group was 17, and 41% were women. Of these, 57% started medication, with methylphenidate being the most common drug. 

The researchers compared people who had started medication within three months of diagnosis with those who had not, and assessed the outcomes over two years after diagnosis.

Reduction in the risk of serious outcomes

The results showed that ADHD medication was associated with a significant reduction in the risk of several serious outcomes: suicide attempts decreased by 17%, substance abuse by 15%, traffic accidents by 12%, and criminality by 13%. The effects were even more pronounced in certain subgroups – for example, a 25% reduction in substance abuse and criminality was noted in individuals who had had recurring problems with these issues.

One possible explanation is that the medication leads to reduced impulsivity, which can reduce the risk of crime by curbing aggressive behaviour, as well as improved attention, which can reduce the risk of traffic accidents by reducing distractions,” says the study’s last author, Zheng Chang, a researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. He continues:

“These results provide evidence that ADHD medication can affect important health and societal outcomes, which should be taken into account both in clinical practice and in the public debate on drug treatment.”

The study is a collaboration between Karolinska Institutet and the University of Southampton. The study was funded by the Swedish Research Council and the Swedish Research Council for Health, Working Life and Welfare, Forte, among others. Some researchers have received fees from pharmaceutical companies, but for work outside the current study.

Source: Karolinska Institutet

Categories : AgeingTags : Leave a comment

Centenarians Develop Diseases More Slowly

On By ModernMedia
Photo by Tim Kilby on Unsplash

Reaching the age of 100 does not necessarily mean a life fraught with illness. A new study from Karolinska Institutet shows that centenarians not only live longer, they also stay healthier than other older people, with fewer diseases that develop more slowly.

The study, published in eClinicalMedicine, compared people who reached the age of 100 with those who died earlier. The results show that centenarians not only suffer from fewer diseases, they also develop them more slowly.

While many older people accumulate several diagnoses quickly during their final years, the disease burden of centenarians seems to level off from around the age of 90. They more often have diseases that are limited to a single organ system and significantly fewer concurrent conditions.

The study also shows that cardiovascular disease is less common and occurs later in life among centenarians. Neuropsychiatric diseases are also less prevalent among those who live the longest.

”Our results challenge the widespread belief that a longer life inevitably means more diseases. We show that centenarians follow a distinct ageing curve, with slower disease progression and greater resistance to common age-related diseases,” says last author Karin Modig, associate professor at the Institute of Environmental Medicine, Karolinska Institutet.

Ages in a different ways

The study covered the entire Swedish birth cohort between 1920 and 1922, totalling over 270,000 individuals. The researchers followed the participants’ health from the age of 70 and up to three decades. The progression of disease in centenarians was compared with those who lived shorter lives using national health registers. The results show that centenarians not only delay disease – they seem to age in a fundamentally different way.

”We show that exceptional longevity is not just about delaying ill health. It reflects a unique pattern of ageing. The results suggest that centenarians have preserved homeostasis and resistance to disease despite ageing and physiological stresses – something that may be due to a favourable combination of genes, lifestyle and environment,” says Karin Modig.

The study was funded by Karolinska Institutet. No conflicts of interest have been reported.

Publikation

”Disease accumulation and distribution across the lifespan in Swedish centenarians and non-centenarians: a nationwide life course comparison of longevity and health resilience”, Yuge Zhang, Shunsuke Murata, Katharina Schmidt-Mende, Marcus Ebeling, Karin Modig, eClinicalMedicine, online August 4, 2025, doi: 10.1016/j.eclinm.2025.103396

Source: Karolinska Institutet