Ozempic Mechanisms - Smelling Cancer -Autism Genes - Heat & Brain

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Jun 26, 2024, 8:10:05 AMJun 26

https://www.scientificamerican.com/article/ozempic-quiets-food-noise-in-the-brain-but-how/

Ozempic Quiets Food Noise in the Brain—But How?

By Lauren J. Young

Kimberly Chauche, a corporate secretary in Lincoln, Neb., says she’s always been overweight. When she was as young as five years old, her doctors started trying to figure out why. Since then her life has involved nutritionists and personal trainers, and eventually she sought therapists to treat her compulsive eating and weight-related anxiety. Yet answers never arrived, and solutions never lasted.

At 43, Chauche was prescribed a weight-loss medication called Wegovy—one of a new class of drugs that mimic a hormone responsible for insulin production. She took her first dose in March 2024, injecting it into herself with a needle. Within a couple of months she had lost almost 20 pounds, and that felt great. But the weight loss seemed like a bonus compared with a startling change in how she reacted to food.

She noticed the shift almost immediately: One day her son was eating popcorn, a snack she could never resist, and she walked right past the bowl. “All of a sudden it was like some part of my brain that was always there just went quiet,” she says. Her eating habits improved, and her anxiety eased. “It felt almost surreal to put an injector against my leg and have happen in 48 hours what decades of intervention could not accomplish,” she says. “If I had lost almost no weight, just to have my brain working the way it’s working, I would stay on this medication forever.”

Chauche is hardly alone in her effusive descriptions of how Wegovy vanquished her intrusive thoughts about food—an experience increasingly referred to as the “quieting of food noise.” Researchers—some of whom ushered in the development of these blockbuster drugs—want to understand why.

Among them is biochemist Svetlana Mojsov of the Rockefeller University, who has spent about 50 years investigating gut hormones that could be key to regulating blood glucose levels. In seeking potential treatments for type 2 diabetes, Mojsov ultimately focused on one hormone: glucagonlike peptide 1, or GLP-1. Her sequence of the protein in the 1980s became the initial template for drugs like Wegovy. The medications, called GLP-1 receptor agonists, use a synthetic version of the natural substance to activate the hormone’s receptors. The first ones arrived in 2005. In 2017 the U.S. Food and Drug Administration approved semaglutide—now widely known as Ozempic.

https://www.sciencenews.org/article/honeybees-smell-lung-cancer

Honeybees can “smell” lung cancer

By Meghan Rosen

Float like a butterfly, sniff out cancer like a bee?

Honeybees can detect the subtle scents of lung cancer in the lab — and even the faint aroma of disease that can waft from a patient’s breath.

Inspired by the insects’ exquisite olfactory abilities, scientists hooked the brains of living bees up to electrodes, passed different scents under the insects’ antennae and then recorded their brain signals. “It’s very clear — like day and night — whether [a bee] is responding to a chemical or not,” says Debajit Saha, a neural engineer at Michigan State University in East Lansing.

Different odors sparked recognizable brain activity patterns, a kind of neural fingerprint for scent, Saha and colleagues report June 4 in Biosensors and Bioelectronics. One day, he says, doctors might be able to use honeybees in cancer clinics as living sensors for early disease detection.

Electronic noses, or e-noses, and other types of mechanical odor-sensing equipment exist, but they’re not exactly the bee’s knees. When it comes to scent, Saha says, “biology has this ability to differentiate between very, very similar mixtures, which no other engineered sensors can do.”

Scent is an important part of how many insect species communicate, says chemical ecologist Flora Gouzerh of the French National Research Institute for Sustainable Development in Montpellier. For them, “it’s a language,” she says.

The idea that animal senses can get a whiff of disease is nothing new; doctors reported a case of a border collie and a Doberman sniffing out their owner’s melanoma in 1989. More recently, scientists have shown that dogs can detect COVID-19 cases by smelling people’s sweat (SN: 6/1/22). A lot of insects probably have disease-detecting abilities, too, Gouzerh says. Ants, for instance, can be trained to pick out the smell of cancer cells grown in a lab dish. But until now, bees’ abilities haven’t been quite so clear, she says.

https://www.thetransmitter.org/spectrum/giant-analysis-reveals-how-autism-linked-genes-affect-brain-cell-types/

Giant analysis reveals how autism-linked genes affect brain cell types

By Charles Q. Choi

The largest-yet single-cell genomics analysis reveals new details of the molecular pathways and cell types that are altered in the cortex in people with autism. The work, published last month in Science, also hints at how genes linked to the condition contribute to these brain differences.

The findings are part of a package of 14 new papers from PsychENCODE, a multi-institution consortium launched in 2015 to study the molecular basis of neuropsychiatric conditions. The initiative’s latest phase of research analyzed human brains at the single-cell level instead of relying on bulk tissue samples as in previous efforts.

“Single-cell analysis gives you the ability to really understand a condition in terms of cell-cell interactions, and how a condition might affect different cell types in very different ways,” says PsychENCODE chair Daniel Geschwind, professor of human genetics, neurology and psychiatry at the University of California, Los Angeles, who led the new autism study.

Past work by Geschwind and others identified a “molecular signature” in tissue samples of autism brains, characterized by increased expression of immune signaling genes, decreased activity of synaptic and neuronal genes, and a reduction in the regional gene-expression patterns typically seen across the cortex. The first single-cell analysis—involving cells from 15 autistic and 16 non-autistic people, and published in 2019—hinted at a role for microglia and excitatory neurons in layer 2/3 of the cortex.

The new study confirms these previous findings and expands autism’s molecular signature to include a subtype of interneurons and layer 5/6 excitatory neurons, which project to other cortical areas. It also adds gene-expression changes, such as heightened immune responses in oligodendrocytes, cells that help produce the myelin sheath insulating the central nervous system. “That suggests there may be something going on broadly with connectivity in autism,” Geschwind says.

https://www.nytimes.com/2024/06/19/well/mind/heat-affect-brain-emotions.html

How Heat Affects the Brain

By Dana G. Smith

In July 2016, a heat wave hit Boston, with daytime temperatures averaging 92 degrees for five days in a row. Some local university students who were staying in town for the summer got lucky and were living in dorms with central air-conditioning. Other students, not so much — they were stuck in older dorms without A.C.

Jose Guillermo Cedeño Laurent, a Harvard researcher at the time, decided to take advantage of this natural experiment to see how heat, and especially heat at night, affected the young adults’ cognitive performance. He had 44 students perform math and self-control tests five days before the temperature rose, every day during the heat wave, and two days after.

“Many of us think that we are immune to heat,” said Dr. Cedeño, now an assistant professor of environmental and occupational health and justice at Rutgers University. “So something that I wanted to test was whether that was really true.”

It turns out even young, healthy college students are affected by high temperatures. During the hottest days, the students in the un-air-conditioned dorms, where nighttime temperatures averaged 79 degrees, performed significantly worse on the tests they took every morning than the students with A.C., whose rooms stayed a pleasant 71 degrees.

A heat wave is once again blanketing the Northeast, South and Midwest. High temperatures can have an alarming effect on our bodies, raising the risk for heart attacks, heatstroke and death, particularly among older adults and people with chronic diseases. But heat also takes a toll on our brains, impairing cognition and making us irritable, impulsive and aggressive.

Numerous studies in lab settings have produced similar results to Dr. Cedeño’s research, with scores on cognitive tests falling as scientists raised the temperature in the room. One investigation found that just a four-degree increase — which participants described as still feeling comfortable — led to a 10 percent average drop in performance across tests of memory, reaction time and executive functioning.

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https://www.npr.org/sections/shots-health-news/2024/06/26/g-s1-6177/brain-waste-removal-system-amyloid-alzheimer-toxins

The brain makes a lot of waste. Now scientists think they know where it goes

Jon Hamilton

About 170 billion cells are in the brain, and as they go about their regular tasks, they produce waste — a lot of it. To stay healthy, the brain needs to wash away all that debris. But how exactly it does this has remained a mystery.

Now, two teams of scientists have published three papers that offer a detailed description of the brain's waste-removal system. Their insights could help researchers better understand, treat and perhaps prevent a broad range of brain disorders.

The papers, all published in the journal Nature, suggest that during sleep, slow electrical waves push the fluid around cells from deep in the brain to its surface. There, a sophisticated interface allows the waste products in that fluid to be absorbed into the bloodstream, which takes them to the liver and kidneys to be removed from the body.

One of the waste products carried away is amyloid, the substance that forms sticky plaques in the brains of patients with Alzheimer's disease.
This illustration demonstrates how the thin film of sensors could be applied to the brain during surgery.

There's growing evidence that in Alzheimer's disease, the brain's waste-removal system is impaired, says Jeffrey Iliff, who studies neurodegenerative diseases at the University of Washington but was not a part of the new studies.

The new findings should help researchers understand precisely where the problem is and perhaps fix it, Iliff says.

"If we restore drainage, can we prevent the development of Alzheimer's disease?" he asks.

The new studies come more than a decade after Iliff and Dr. Maiken Nedergaard, a Danish scientist, first proposed that the clear fluids in and around the brain are part of a system to wash away waste products.

The scientists named it the glymphatic system, a nod to the body's lymphatic system, which helps fight infection, maintain fluid levels and filter out waste products and abnormal cells.

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https://www.nature.com/articles/d41586-024-02069-2

Spinal cord ‘atlas’ offers unprecedented insights into injuries

By Miryam Naddaf

Researchers have developed a four-dimensional model of spinal-cord injury in mice, which shows how nearly half a million cells in the spinal cord respond over time to injuries of varying severity. The model, known as a cell atlas, could help researchers to resolve outstanding questions and develop new treatments for people with spinal-cord injury (SCI).

“If you know what every single cell on the spinal cord is doing in response to injury, you could use that knowledge to develop tailor-made and mechanism-based therapies,” says Mark Anderson, a neurobiologist at the Swiss Federal Institute of Technology in Geneva, Switzerland, who worked on the atlas. “Things don’t need to be a shot in the dark.”

Anderson and his colleagues used machine-learning algorithms to build the atlas by mapping data from RNA sequencing and other cell-biology techniques. They described the work in a Nature paper published today1 and have made the entire atlas available through an online platform.

The atlas is a valuable resource for testing hypotheses about SCI, says Binhai Zheng, who studies spinal-cord regeneration at the University of California, San Diego. “There are a lot of hidden treasures.”

The researchers examined sections of the spinal cord, sampled from 52 injured and uninjured mice at 1, 4, 7, 14, 30 and 60 days after injury. Their analysis involved 18 experimental SCI conditions, including different types of injury and levels of severity. They used RNA-sequencing tools to explore how 482,825 cells responded to injury over time.