Thursday, May 22, 2025

 

Habitat and humans shaped sloth evolution and extinction


Summary author: Walter Beckwith


American Association for the Advancement of Science (AAAS)





Ancient sloths ranged in size from tiny climbers to ground-dwelling giants. Now, researchers report this body size diversity was largely shaped by sloths’ habitats, and that these animals’ precipitous decline was likely a result of increasing human pressures, which also triggered the extinction of the large-bodied ground-dwelling animals. Today’s small arboreal sloths are the last remnants of a once-diverse group, surviving likely because they inhabited secluded forest canopies and avoided direct human pressures, say the authors. While only two small, tree-dwelling genera survive today – confined largely to the tropical rainforests of South and Central America – sloths (Folivora) represent a once-diverse, abundant, and widespread lineage of American mammals. During the late Cenozoic, more than 100 genera of sloths occupied a wide range of sizes and habitats, living across the Americas. Some terrestrial sloth species stood upwards of six meters tall and weighed several tons. However, by the end of the Pleistocene, the majority of these animals became extinct.

 

Alberto Boscaini and colleagues investigated the drivers behind the expansion and decline of body size variation in sloths over the past 35 million years, culminating in the eventual rapid collapse of the group. By combining fossil measurements, DNA and protein sequences, and advanced evolutionary modeling, Boscaini et al. reconstructed sloth evolutionary history across 67 genera and tested whether evolutionary changes in size were linked to habitat, diet, climate, predation, or other ecological pressures. The findings show that habitat preference – whether sloths lived in trees or on the ground – was the dominant factor shaping their body size evolution. Early sloths were large, ground-dwelling grazers. But transitions to tree-dwelling forms with smaller body sizes occurred multiple times, especially as open landscapes expanded. Gigantism evolved independently in several lineages, reflecting adaptive responses to cooling climates and ecological pressures. Yet, despite thriving for tens of millions of years, with body size diversity peaking in the Pleistocene, sloths experienced a sudden and dramatic decline beginning around 15,000 years ago. These declines do not align with the climatic changes of the time, but instead with the arrival of humans in the Americas. According to Boscaini et al., evidence suggests that human hunting drove the extinction of large-bodied terrestrial sloths.

 

For reporters interested in trends, a March 2019 Science Advances study by Gustavo Politis et al. highlights direct archaeological evidence of human giant sloth hunting and butchering in the Argentinian Pampas roughly 12,000 years ago.

Scientists have figured out how extinct giant ground sloths got so big and where it all went wrong





Florida Museum of Natural History

Image 1 

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Ancient sloths lived in trees, on mountains, in deserts, boreal forests and open savannahs. These differences in habitat are primarily what drove the wide difference in size between sloth species.

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Credit: Illustration by Diego Barletta





Most of us are familiar sloths, the bear-like animals that hang from trees, live life in the slow lane, take a month to digest a meal and poop just once a week. Their closest living relatives are anteaters and armadillos, and if that seems like an odd pairing, there’s a reason why. Today, there are only two sloth species, but historically, there were dozens of them, including one with a bottle-nosed snout that ate ants and another that likely resembled the ancestors of modern armadillos.

Most of these extinct sloths also didn’t live in trees, because they were too big. The largest sloths, in the genus Megatherium, were about the size of Asian bull elephants and weighed roughly 8,000 pounds.

“They looked like grizzly bears but five times larger,” said Rachel Narducci, collection manager of vertebrate paleontology at the Florida Museum of Natural History.

Narducci is co-author of a new study published in the journal Science in which scientists analyzed ancient DNA and compared more than 400 fossils from 17 natural history museums to figure out how and why extinct sloths got so big.

Ground sloths varied widely in size, from the truly massive Megatherium — which could rip foliage off the tops of trees with its prehensile tongue and acted as a sort of ecological stand in for giraffes — to the modestly chunky Shasta ground sloth that terrorized cacti in the desert southwest of North America.

The same cannot be said for sloths that developed an affinity for tree climbing. Those that lived entirely in the canopy were and are uniformly small, with an average weight of 14 pounds, while those that spent part of their time on the ground averaged about 174 pounds. 

You don’t have to be a scientist to puzzle out why trees enforce a strict weight limit. It’s the same reason why modern tree sloths have a strange elastic quality to them: Branches break when put under too much strain, and sloths are not generally known for their ability to swiftly avert sudden disaster. Tree sloths have reportedly survived falls of up to 100 feet. However, given that falls from even moderate heights can cause severe damage and some trees in the Amazon Rainforest top out at just under 300 feet, it makes evolutionary sense to be as small as possible when going out on a limb.

What’s less clear is why some ground sloths grew to such excessive sizes while others seemed content with being merely large. There may have been several reasons, which is why it’s been so hard for scientists to answer the question with confidence.

Larger sizes might have been advantageous for finding food or avoiding predators, for example. Ground sloths had a special fondness for caves, and their size undoubtedly played a role in their ability to find and make shelters. The moderately sized Shasta ground sloth favorited small, natural caves bored by wind and water into the cliffsides of the Grand Canyon, like the alveoli of a gigantic, geologic lung. These also doubled as convenient latrines; in 1936, paleontologists discovered a mound of fossilized sloth poop, bat guano and packrat middens more than 20 feet thick in Rampart Cave, near Lake Mead.

Larger sloths weren’t restricted to pre-existing caves. Using claws that are among the largest of any known mammal, living or extinct, they could carve their own from bare earth and rock. Many of the caves they left behind are still around with claw-mark décor along the interior walls, evidence of their ancient nesting excavations.

Other factors that may have contributed to their size discrepancy include climate, the degree of relatedness among sloth species and metabolic rates. The ability to accurately discriminate between these several possibilities required a substantial amount and various types of data.

The authors combined information about the shape of fossils with DNA from living and extinct species to create a sloth tree of life that traced the sloth lineage all the way back to their origin more than 35 million years ago. With this scaffold in place, they added results gleaned from decades of research about where sloths lived, what they ate and whether they were climbers or walkers. Because the authors were specifically interested in the evolution of size, they collected data for the final analytical ingredient by measuring hundreds of museum fossils, which they used to estimate sloth weight.

This is where the Florida Museum played a special role. “We have the largest collection of North American and Caribbean-island sloths in the world,” Narducci said. She carefully took several measurements of 117 limb bones and shared the numbers with her colleagues.

The authors mixed all this information together, computationally stirred it and got back a fully baked answer.

The result: Size differences among sloths has been primarily influenced by the types of habitats they lived in and, by extension, climate change.

“Including all of these factors and running them through evolutionary models with multiple different scenarios was a major undertaking that had not been done before,” Narducci said.

The sloth dynasty coincided with significant, life-altering changes in Earth’s climate. The oldest thing that scientists can reasonably consider to be a sloth is called Pseudoglyptodon, which lived 37 million years ago in Argentina. Analyses from the study indicate the earliest sloths would have likely been small ground dwellers, about the size of a great Dane. At various points throughout their evolutionary history, sloths adopted a semi-arboreal lifestyle. Not all of them stayed in the trees, however. The largest sloths, including Megatherium and Mylodon, likely evolved from a tree-adapted sloth that ultimately decided to stay firmly planted on the ground.

Against this background of indecisive climbers and walkers, the size of sloths hardly changed at all for about 20 million years, irrespective of their preferred method of locomotion. Then something earth-shattering occurred.

A giant wound opened up between modern-day Washington state and Idaho down through parts of Oregon and Nevada, and magma boiled out of it. This left a nearly 600,000 cubic mile scab over the Pacific Northwest. It’s still visible in some places along the Columbia River, where millions of years of running water have cut through and polished a colonnade of basalt. These rock pillars have a distinct hexagonal shape caused by the way in which the magma hardened and cracked as it cooled. The volcanic event that made them was a slow burn that lasted roughly 750,000 years and aligned with a period of global warming called the Mid-Miocene Climatic Optimum. The greenhouse gasses emitted by the volcanic eruption are currently considered the likeliest cause of the warming.

Sloths responded by getting smaller. This may be because warmer temperatures brought increased precipitation, which allowed forests to expand, thereby creating more habitat for smaller sloths. Size reduction is also a common way for animals to deal with heat stress and has been documented in the fossil record on several different occasions.

The world remained warm for about a million years after the volcano fell silent. Then, the planet resumed a longstanding pattern of cooling that has continued in fits and starts to the present. Sloths reversed course too. The more temperatures fell, the bulkier they became.

Arboreal and semi-arboreal sloths had the obvious limitation of having to live near trees, but ground sloths lived just about anywhere their feet would take them. They climbed the Andes Mountains, fanned out through open savannahs, migrated into the deserts and deciduous forests of North America and made a home for themselves in the boreal forests of Canada and Alaska. There were even sloths adapted to marine environments. Thalassocnus lived in the arid strip of land between the Andes and the Pacific. They survived in this harsh region by foraging for food in the ocean.

“They developed adaptations similar to those of manatees,” Narducci said. “They had dense ribs to help with buoyancy and longer snouts for eating seagrass.”

These varied environments presented unique challenges that ground sloths met, in part, by beefing up. “This would’ve allowed them to conserve energy and water and travel more efficiently across habitats with limited resources,” Narducci said. “And if you’re in an open grassland, you need protection, and being bigger provides some of that. Some ground sloths also had little pebble-like osteoderms embedded in their skin,” Narducci said, referencing the bony plating that sloths had in common with their armadillo relatives, a trait that was also recently discovered in spiny mice.

Equally as important, larger bodies helped sloths contend with cooling climates. They reached their greatest stature during the Pleistocene ice ages, shortly before they disappeared.

“About 15,000 years ago is when you really start to see the drop-off,” Narducci said.

There’s still debate about what happened to sloths, but given that humans arrived in North America at about the same time sloths went extinct in droves, it’s not hard to speculate. Paradoxically, the large size that kept them safe from most predators and insulated from the cold became a liability. Neither fast nor well-defended, ground and semi-arboreal sloths were easy pickings for early humans.

Arboreal sloths watched the carnage unfold below them from the safety of the treetops, but even there, they didn’t escape without losses. Long after their ground-dwelling relatives had gone extinct everywhere else, two species of tree sloth in the Caribbean held out until 4,500 years ago. Humans arrived in the Caribbean about the same time that Egyptians were building the pyramids. Caribbean tree sloths went extinct not long after.

Alberto Boscaini, Néstor Toledo François Pujos, Eduardo Soto, Sergio Vizcaíno and Ignacio Soto of the Consejo Nacional de Investigaciones Científicas y Técnicas, Daniel Casali, Susana Bargo of the Universidad Nacional de La Plata, Max Langer of the Universidade de São Paulo, Juan L. Cantalapiedra of the Universidad de Alcalá, Gerardo De Iuliis of the University of Toronto and Timothy Gaudin of the University of Tennessee at Chattanooga are also co-authors of the study.

From "non-essential" to life-saver: the spleen’s hidden role as a built-in bioreactor




Nanjing University School of Life Sciences
Human islets grown in the immune-remodeled spleen of macaques 

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Human islets grown in the immune-remodeled spleen of macaques.

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Credit: Credited by Lei Dong/Nanjing University and Jian Xiao/Wenzhou Medical University




Groundbreaking Discovery

What if the human body contained a natural bioreactor capable of regenerating vital organs? A collaborative team from ​Wenzhou Medical University, Nanjing University, and University of Macau has redefined the spleen’s potential, transforming it into a ​self-sustaining hub for organ regeneration, as published in Science Translational Medicine (May 21). This breakthrough could revolutionize treatments for type 1 diabetes and beyond.

Redesigning the Spleen: From Filter to "Living Bioreactor"

Confronting the dual challenges of poor islet survival and immune rejection in traditional transplants, researchers posed a bold question: Could we repurpose an underutilized organ to nurture new life?

Led by ​Prof. Lei Dong and Prof. Jian Xiao, the team engineered ​smart nanoparticles to reprogram the spleen’s microenvironment. "We’re essentially converting the spleen into a high-performance bioreactor," Dong explains. "By enhancing extracellular matrix support, accelerating blood vessel growth, and suppressing immune attacks, we’ve created an ideal niche for transplanted cells to thrive."

In a landmark achievement, ​human islet tissues successfully matured within the reprogrammed spleens of cynomolgus macaques, demonstrating compatibility with both human and animal-derived cells. This dual success paves the way for addressing organ shortages through cross-species solutions.

 

Why the Spleen? Three Biological Superpowers

Ample Space: A porous structure capable of hosting billions of cells

Nutrient-Rich Network: Direct blood supply to the liver’s portal vein mimics natural organ development

Low-Risk Adaptation: Remodeling occurs without disrupting critical bodily functions

 

Proven Track Record: Regenerating Organs Within the Body

The team’s spleen-based regeneration platform has achieved multiple milestones:

Functional Liver (Science Advances, 2020): Reprogrammed mouse spleens to perform liver functions

In Situ Regeneration (Gut, 2022)Grew liver tissues using gene editing, bypassing cell transplants

Thyroid Restoration (Advanced Science, 2024)Rebuilt hormone-producing tissues in animal models

 

Future Vision: A Personalized Organ Nursery

Next goal? ​Growing patient-specific organs from induced pluripotent stem cells (iPSCs). "The spleen acts like a living bioreactor embedded in our bodies," Dong describes. "With minimally invasive B-ultrasound-guided delivery, we could one day cultivate custom-made organs on demand."

While clinical applications require rigorous safety validation, this discovery challenges conventional wisdom. Once deemed "non-essential," the spleen now emerges as nature’s ultimate toolkit for regenerative medicine—proving that life’s most powerful solutions may have been inside us all along.

Macaque used for spleen transformation.

Mouse spleen transformed into a liver 

Mouse spleen transformed into a liver. Science Advances, 2020, DOI: 10.1126/sciadv.aaz9974.

Thyroid Restoration with vascular network in the spleen. Advanced Science, 2024, DOI: 10.1002/advs.202305913.

Credit

Credited by Lei Dong/Nanjing University and Jian Xiao/Wenzhou Medical 

 

A new approach could fractionate crude oil using much less energy



MIT researchers’ new membrane separates different types of fuel based on their molecular size, eliminating the need for energy-intensive crude oil distillation.





Massachusetts Institute of Technology

Membrane filter 

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MIT engineers developed a membrane, pictured, that filters the components of crude oil by their molecular size, an advance that could dramatically reduce the amount of energy needed for crude oil fractionation.

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Credit: MIT




CAMBRIDGE, MA -- Separating crude oil into products such as gasoline, diesel, and heating oil is an energy-intensive process that accounts for about 6 percent of the world’s CO2 emissions. Most of that energy goes into the heat needed to separate the components by their boiling point.

In an advance that could dramatically reduce the amount of energy needed for crude oil fractionation, MIT engineers have developed a membrane that filters the components of crude oil by their molecular size.

“This is a whole new way of envisioning a separation process. Instead of boiling mixtures to purify them, why not separate components based on shape and size? The key innovation is that the filters we developed can separate very small molecules at an atomistic length scale,” says Zachary P. Smith, an associate professor of chemical engineering at MIT and the senior author of the new study.

The new filtration membrane can efficiently separate heavy and light components from oil, and it is resistant to the swelling that tends to occur with other types of oil separation membranes. The membrane is a thin film that can be manufactured using a technique that is already widely used in industrial processes, potentially allowing it to be scaled up for widespread use.

Taehoon Lee, a former MIT postdoc who is now an assistant professor at Sungkyunkwan University in South Korea, is the lead author of the paper, which appears today in Science.

Oil fractionation

Conventional heat-driven processes for fractionating crude oil make up about 1 percent of global energy use, and it has been estimated that using membranes for crude oil separation could reduce the amount of energy needed by about 90 percent. For this to succeed, a separation membrane needs to allow hydrocarbons to pass through quickly, and to selectively filter compounds of different sizes.

Until now, most efforts to develop a filtration membrane for hydrocarbons have focused on polymers of intrinsic microporosity (PIMs), including one known as PIM-1. Although this porous material allows the fast transport of hydrocarbons, it tends to excessively absorb some of the organic compounds as they pass through the membrane, leading the film to swell, which impairs its size-sieving ability. 

To come up with a better alternative, the MIT team decided to try modifying polymers that are used for reverse osmosis water desalination. Since their adoption in the 1970s, reverse osmosis membranes have reduced the energy consumption of desalination by about 90 percent — a remarkable industrial success story.

The most commonly used membrane for water desalination is a polyamide that is manufactured using a method known as interfacial polymerization. During this process, a thin polymer film forms at the interface between water and an organic solvent such as hexane. Water and hexane do not normally mix, but at the interface between them, a small amount of the compounds dissolved in them can react with each other.

In this case, a hydrophilic monomer called MPD, which is dissolved in water, reacts with a hydrophobic monomer called TMC, which is dissolved in hexane. The two monomers are joined together by a connection known as an amide bond, forming a polyamide thin film (named MPD-TMC) at the water-hexane interface.

While highly effective for water desalination, MPD-TMC doesn’t have the right pore sizes and swelling resistance that would allow it to separate hydrocarbons.

To adapt the material to separate the hydrocarbons found in crude oil, the researchers first modified the film by changing the bond that connects the monomers from an amide bond to an imine bond. This bond is more rigid and hydrophobic, which allows hydrocarbons to quickly move through the membrane without causing noticeable swelling of the film compared to the polyamide counterpart.

“The polyimine material has porosity that forms at the interface, and because of the cross-linking chemistry that we have added in, you now have something that doesn’t swell,” Smith says. “You make it in the oil phase, react it at the water interface, and with the crosslinks, it’s now immobilized. And so those pores, even when they’re exposed to hydrocarbons, no longer swell like other materials.”

The researchers also introduced a monomer called triptycene. This shape-persistent, molecularly selective molecule further helps the resultant polyimines to form pores that are the right size for hydrocarbons to fit through.

Efficient separation

When the researchers used the new membrane to filter a mixture of toluene and triisopropylbenzene (TIPB) as a benchmark for evaluating separation performance, it was able to achieve a concentration of toluene 20 times greater than its concentration in the original mixture. They also tested the membrane with an industrially relevant mixture consisting of naphtha, kerosene, and diesel, and found that it could efficiently separate the heavier and lighter compounds by their molecular size.

If adapted for industrial use, a series of these filters could be used to generate a higher concentration of the desired products at each step, the researchers say.

“You can imagine that with a membrane like this, you could have an initial stage that replaces a crude oil fractionation column. You could partition heavy and light molecules and then you could use different membranes in a cascade to purify complex mixtures to isolate the chemicals that you need,” Smith says.

Interfacial polymerization is already widely used to create membranes for water desalination, and the researchers believe it should be possible to adapt those processes to mass produce the films they designed in this study.

“The main advantage of interfacial polymerization is it’s already a well-established method to prepare membranes for water purification, so you can imagine just adopting these chemistries into existing scale of manufacturing lines,” Lee says.

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The research was funded, in part, by ExxonMobil through the MIT Energy Initiative.


Even weak tropical cyclones raise infant mortality in poorer countries, USC-led research finds


A new study finds that even storms below hurricane strength significantly increase infant deaths in low- and middle-income countries, and not just for the reasons experts expected.



University of Southern California





Tropical cyclones, including storms below hurricane and typhoon strength, were associated with a sharp rise in infant mortality in low- and middle-income countries during the first two decades of this century, according to new research published in Science Advances. The findings point to a critical need for stronger disaster response and child health protections in vulnerable regions, especially as climate change increases the frequency and severity of these storms.

Infants in these regions exposed to tropical cyclones before they were born or during their first year of life were significantly more likely to die: Infant mortality rose an average of 11% over baseline rates — an increase of 4.4 deaths per 1,000 live births.

The risk was greatest in the first year after a storm and did not appear to persist beyond two years after.

Surprisingly, the increase in mortality could not be explained by reduced access to prenatal care or worsening nutrition, two commonly cited health risks following natural disasters. “The fact that health care use and undernutrition were not affected by tropical cyclone exposure suggests that the mortality effects are driven by other factors that we could not directly study,” said lead author Zachary Wagner, associate professor (research) of economics at the USC Dornsife College of Letters, Arts and Sciences and senior economist at the College’s Center for Economic and Social Research. “We have a lot more research to do to uncover these main drivers.”

The study team — which included researchers from RAND Corporation, Stanford University, Johns Hopkins University and Belgium’s UCLouvain — found that the increased mortality followed not just the most intense storms but also lower-intensity tropical storms, which are far more common.

“Some of the countries had only a few Category 3 or higher storms during the period we studied,” said Zetianyu Wang, a PhD student under Wagner at RAND and first author on the report. This made it more difficult to detect clear links between the most intense storms and infant deaths. “But that doesn’t mean the impact of larger storms is absent. As the planet warms, we risk more tragedies across the globe if measures aren’t taken to protect children in the poorest countries.”

Storm effects varied widely among countries

The researchers analyzed nearly 1.7 million child records from seven economically disadvantaged countries: Madagascar, India, Bangladesh, Cambodia, the Philippines, the Dominican Republic and Haiti.

While the average increase in infant mortality across all of these countries was 11%, the impact of storms varied significantly from country to country. In Bangladesh, Haiti and the Dominican Republic, cyclones were followed by increases of more than 10 deaths per 1,000 births. In contrast, little to no increase in mortality was observed in India, the Philippines, Cambodia and Madagascar. The researchers say it remains unclear why some countries fare better than others. The differences may reflect varying levels of disaster preparedness, geographic vulnerability, or underlying public health conditions.

“Some countries may be helped by mountains while others have more flood-prone areas,” Wagner said. “Some countries have better systems in place for evacuation efforts, or they may have sturdier housing while others rely on thatched roofs. And in some places, children may already be malnourished or in poor health from malaria and other diseases, which increases vulnerability.”

Understanding the reasons behind the differences, Wagner says, will be a key focus of future research.

“If we want to protect children from the growing threat of climate-linked disasters,” he said, “we need to understand not just where risk is greatest, but why.”

About this study

In addition to Wagner and Wang, authors on the study include Renzhi Jing, Sam Heft-Neal and Eran Bendavid of Stanford University; Aaron Clark-Ginsberg of RAND; and Debarati Guha-Sapir of UC Louvain and Johns Hopkins University.

 


 

New ketamine study promises extended relief for depression


BETTER LIVING THROUGH CHEMISTRY


Breakthrough study suggests promising method to extend the antidepressant action of ketamine against major depression for weeks



Vanderbilt University





Roughly 10 percent of the U.S. population is afflicted with major depressive disorder at any given time, and up to 20 percent will exhibit MDD symptoms over their lifetimes.

Yet despite its prevalence, methods to treat MDD often fall short for a not-insignificant portion of the population. Antidepressants—the standard of treatment—don’t work for 30 percent with MDD.

When infused at a low dose ketamine shows remarkable efficacy as a rapidly acting antidepressant, with effects observed within hours even in patients who have been resistant to other antidepressant treatments. However, consistent infusions of ketamine are needed to maintain symptoms at bay, which could result in side effects, such as dissociative behaviors and the possibility of addiction, and stopping treatment can result in relapse.

In a new study published in ScienceLisa Monteggia’s and Ege Kavalali’s labs show that it is feasible to substantially extend the efficacy of a single dose of ketamine from its current duration of up to a week to a longer period of up to two months.

 “The premise of this study, which was led by Zhenzhong Ma, a fantastic research assistant professor, was based on a testable mechanistic model that we developed that accounts for ketamine’s rapid antidepressant action,” Monteggia said. Monteggia holds the Lee E. Limbird Chair in Pharmacology and is the Barlow Family Director of the Vanderbilt Brain Institute.

Previously, researchers in the field had determined that ketamine’s antidepressant effect requires the activation of a key signaling pathway called ERK, but only ketamine’s long-term effects—not its rapid effects—are abolished when ERK is inhibited. As a fast-acting antidepressant, ketamine relies on ERK-dependent synaptic plasticity to produce its rapid behavioral effects. Ma and colleagues hypothesized that they could maintain ketamine’s effects for longer periods by enhancing ERK activity.

In the recent paper, Ma discovered that ketamine’s antidepressant effects could be sustained for up to two months by using a drug called BCI, which inhibits a protein phosphatase and results in increased ERK activity. By inhibiting the phosphatase, the authors retained ERK’s activity and augmented the synaptic plasticity that drives ketamine’s prolonged antidepressant effects.

Although the use of BCI make the application of these results to the clinic difficult, Monteggia said that the results provide a proof of principle that ketamine's antidepressant action can be sustained by targeting intracellular signaling. She and Kavalali, the William Stokes Professor of Experimental Therapeutics and the chair of the Department of Pharmacology, have worked on the project since its inception and hope that it fosters other studies looking to identify specific molecules that will enhance and sustain the action of a single dose of ketamine.

Ultimately, this work will be a steppingstone toward improving MDD patients’ lives by reducing the burden of treatment.

Graduate student Natalie Guzikowski and postdoctoral fellow Ji-Woon Kim were coauthors on the study.