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Category: neuroscience – Page 113

Total Synthesis and Anticancer Study of (+)-Verticillin AClick to copy article linkArticle link copied!

For the first time, MIT chemists have synthesized a fungal compound known as verticillin A, which was discovered more than 50 years ago and has shown potential as an anticancer agent.

The compound has a complex structure that made it more difficult to synthesize than related compounds, even though it differed by only a couple of atoms.

“We have a much better appreciation for how those subtle structural changes can significantly increase the synthetic challenge,” says Mohammad Movassaghi, an MIT professor of chemistry. “Now we have the technology where we can not only access them for the first time, more than 50 years after they were isolated, but also we can make many designed variants, which can enable further detailed studies.”

In tests in human cancer cells, a derivative of verticillin A showed particular promise against a type of pediatric brain cancer called diffuse midline glioma. More tests will be needed to evaluate its potential for clinical use, the researchers say.

Movassaghi and Jun Qi, an associate professor of medicine at Dana-Farber Cancer Institute/Boston Children’s Cancer and Blood Disorders Center and Harvard Medical School, are the senior authors of the study, which appears today in the Journal of the American Chemical Society. Walker Knauss PhD ’24 is the lead author of the paper. Xiuqi Wang, a medicinal chemist and chemical biologist at Dana-Farber, and Mariella Filbin, research director in the Pediatric Neurology-Oncology Program at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center, are also authors of the study.

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Synthetic neuroscience grants promote transformative brain tech

The Wu Tsai Neurosciences Institute, Sarafan ChEM-H, and Stanford Bio-X have awarded $1.24 million in grants to five innovative, interdisciplinary, and collaborative research projects at the intersection of neuroscience and synthetic biology.

The emerging field of synthetic neuroscience aims to leverage the precision tools of synthetic biology — like gene editing, protein engineering, and the design of biological circuits — to manipulate and understand neural systems at unprecedented levels. By creating custom-made biological components and integrating them with neural networks, synthetic neuroscience offers new ways to explore brain function, develop novel therapies for neurological disorders, and even design biohybrid systems that could one day allow brains to interface seamlessly with technology.

“The ongoing revolution in synthetic biology is allowing us to create powerful new molecular tools for biological science and clinical translation,” said Kang Shen, Vincent V.C. Woo Director of the Wu Tsai Neurosciences Institute. “With these awards, we wanted to bring the Stanford neuroscience community together to capitalize on this pivotal moment, focusing the power of cutting-edge synthetic biology on advancing our understanding of the nervous system — and its potential to promote human health and wellbeing.”

‘Brainquake’ phenomenon links psychotic states to chaotic information flow

Some psychiatric disorders, particularly schizophrenia and bipolar disorder (BP), can prompt the emergence of so-called psychotic states, mental states characterized by distorted thinking patterns, altered perceptions and unusual beliefs. Detecting and diagnosing these states is not always easy, as they often overlap with the symptoms of other mental health disorders, and reliable methods to identify psychosis are still lacking.

Researchers at Georgia Institute of Technology and Emory University recently carried out a study aimed at further exploring the neural signatures of psychotic states. Their findings, published in Molecular Psychiatry, suggest that the activity in the brains of individuals who are experiencing psychosis is significantly more random, following patterns that hint at an unstable flow of information.

“The measures of resting-state fMRI spatiotemporal complexity offer a powerful tool for identifying irregularities in brain activity,” Qiang Li, Jingyu Liu, and their colleagues wrote in their paper.

New bioadhesive strategy can prevent fibrous encapsulation around device implants on peripheral nerves

Peripheral nerves—the network connecting the brain, spinal cord, and central nervous system to the rest of the body—transmit sensory information, control muscle movements, and regulate automatic bodily functions. Bioelectronic devices implanted on these nerves offer remarkable potential for the treatment and rehabilitation of neurological and systemic diseases.

However, because the body perceives these implants as foreign objects, they often trigger the formation of dense fibrotic tissue at bioelectronic device–tissue interfaces, which can significantly compromise device performance and longevity.

Molecular switch links early-life stimulation to lasting memory changes

Researchers have identified a molecular mechanism that helps explain why growing up in a stimulating environment enhances memory. In contrast, a lack of stimulation can impair it. The team from the Institute for Neurosciences (IN), a joint research center of the Spanish National Research Council (CSIC) and Miguel Hernández University of Elche (UMH), was led by researcher Ángel Barco.

Their study, conducted in mice and published in Nature Communications, demonstrates that the environment during childhood and adolescence has a lasting impact on the brain by activating or repressing a single transcription factor, AP-1, which regulates the expression of genes involved in neuronal plasticity and learning. This finding identifies a molecular mediator that can translate life experiences into persistent changes in cognitive function.

The ‘silent’ brain cells that shape our behaviour, memory and health

Researchers peered through microscopes, hooked up electrodes, and built entire careers around one cell type: neurons. These electrically active cells were clearly the brain’s protagonists, zipping signals through our heads at lightning speed to create thoughts, memories, and movements. Everything else—especially the star-shaped cells called astrocytes that outnumber neurons—was dismissed as mere scaffolding. Glial cells, they were called: “glue.”

Inbal Goshen, a memory researcher at Hebrew University of Jerusalem, remembers feeling like an outsider when she started investigating astrocytes in the early 2010s. “Oh, that’s the weird one who works on astrocytes,” she imagined colleagues whispering at conferences. The skepticism was palpable. Yet new molecular tools had finally given her a way to peek into these mysterious cells, and what she found was too intriguing to ignore.

Unlike neurons, astrocytes don’t fire electrical signals. They were “electrically silent,” which is why they’d been ignored. But they were whispering in another language entirely: calcium. Using advanced imaging, researchers discovered that astrocytes communicate through slow, rhythmic waves of calcium signals—more like a gentle tide than neuron’s lightning strike. And their reach is astonishing: a single human astrocyte can touch up to two million synapses, the junctions where neurons meet. Their bushy tendrils fill every crevice of the brain, each cell nestling against neurons and blood vessels, creating an intimate, three-way relationship.

Memory research revealed another layer. Goshen’s team watched astrocytes in mice navigating toward water rewards. As the animals approached familiar prize locations, astrocyte activity slowly ramped up—but showed no response in new environments. The cells were encoding spatial memories, not just supporting them. Other labs found that astrocytes help stabilize and recall fear memories, their slow calcium signals perfectly suited to bridge the gap between learning something and remembering it days later. As neuroscientist Jun Nagai describes it, “Think of them as the brain’s long-exposure camera: they capture the trace of meaningful events that might otherwise fade too fast.”

Astrocytes make up one-quarter of the brain, but researchers are only now realizing their true value.

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