Author: Hilary

Is Treatment for Genetic Autism on the Horizon?

Written by Hilary on 25 November 2024. Posted in Newsroom.

New study reveals brain mechanisms involved in genetically based autism which may lead to effective treatment

A groundbreaking study from Tel Aviv University expands the understanding of the biological mechanism underlying genetically-based autism, specifically mutations in the SHANK3gene, responsible for nearly one million cases of autism worldwide. Based on these discoveries, the research team applied a genetic treatment that improved the function of cells affected by the mutation, laying a foundation for future treatments for SHANK3-related autism.

The study was led by the lab of Prof. Boaz Barak and PhD student Inbar Fischer from the Sagol School of Neuroscience and the School of Psychological Sciences at Tel Aviv University, in collaboration with the labs of Prof. Ben Maoz from the Department of Biomedical Engineering at Fleischman Faculty of Engineering at Tel Aviv University and Prof. Shani Stern from the Department of Neurobiology at the University of Haifa. The article was published in the prestigious journal Science Advances.

PhD student Inbar Fischer.

Prof. Barak: “Autism is a relatively common neurodevelopmental disorder. According to current data, 1-2% of the global population and one in every 36 boys in the U.S. are diagnosed with autism spectrum disorder (ASD), with numbers rising over time. Autism is caused by a wide range of factors – environmental, genetic, and even social and cultural (such as the rise in parental age at conception). In my lab, we study the genetic causes of autism. Among these are mutations in a gene called SHANK3. The impact of these mutations on the function of brain neurons has been extensively studied, and we know that the protein encoded by SHANK3 plays a central role in binding receptors in the neuron, essential for receiving chemical signals (neurotransmitters and others) by which neurons communicate. Thus, damage to this gene can disrupt message transmission between neurons, impairing the brain’s development and function. In this study we sought to shed light on other, previously unknown mechanisms, through which mutations in the SHANK3 gene disrupt brain development, leading to disorders manifested as autism”.

Specifically, the research team focused on two components in the brain that have not yet been studied extensively in this context: non-neuronal brain cells (glia) called oligodendrocytes and the myelin they produce. Myelin tissue is a fatty layer that insulates nerve fibers (axons), similar to the insulating layer that coats electrical cables. When the myelin is faulty, the electrical signals transmitted through the axons may leak, disrupting the message transmission between brain regions and impairing brain function.

How a Gene Mutation Impacts the Brain

The team employed a genetically engineered mouse model for autism, introducing a mutation in the Shank3 gene that mirrors the mutation found in humans with this form of autism. Inbar Fischer: “Through this model, we found that the mutation causes a dual impairment in the brain’s development and proper function: first, in oligodendrocytes, as in neurons, the SHANK3 protein is essential for the binding and functioning of receptors that receive chemical signals (neurotransmitters and others) from neighboring cells. This means that the defective protein associated with autism disrupts message transmission to these vital support cells. Secondly, when the function and development of oligodendrocytes is impaired, their myelin production is also disrupted. The faulty myelin does not properly insulate the neuron’s axons, thereby reducing the efficiency of electrical signal transmission between brain cells, as well as the synchronization of electrical activity between different parts of the brain. In our model, we found myelin impairment in multiple brain areas and observed that the animals’ behavior was adversely affected as a result”.

The researchers then sought a method for fixing the damage caused by the mutation, with the hope of ultimately developing a treatment for humans. Inbar Fischer: “We obtained oligodendrocytes from the brain of a mouse with a Shank3 mutation, and inserted DNA segments containing the normal human SHANK3 sequence. Our goal was to allow the normal gene to encode a functional and normal protein, which, replacing the defective protein, would perform its essential role in the cell. To our delight, following treatment, the cells expressed the normal SHANK3 protein, enabling the construction of a functional protein substrate to bind the receptors that receive electrical signals. In other words, the genetic treatment we had developed repaired the oligodendrocytes’ communication sites, essential for the cells’ proper development and function as myelin producers”.

To validate findings from the mouse model, the research team generated induced pluripotent stem cells from the skin cells of a girl with autism caused by a SHANK3 gene mutation identical to that in the mice. From these stem cells, they derived human oligodendrocytes with the same genetic profile. These oligodendrocytes displayed impairments similar to those observed in their mouse counterparts.

Autism and Myelin Damage: New Hope for Treatment

Prof. Barak concludes: “In our study, we discovered two new brain mechanisms involved in genetically induced autism: damage to oligodendrocytes and, consequently, damage to the myelin they produce. These findings have important implications – both clinical and scientific. Scientifically, we learned that defective myelin plays a significant role in autism and identified the mechanism causing the damage to myelin. Additionally, we revealed a new role for the SHANK3 protein: building and maintaining a functional binding substrate for receptors critical for message reception in oligodendrocytes (not just in neurons). We discovered that contrary to the prevailing view, these cells play essential roles in their own right, far beyond the support they provide for neurons — often seen as the main players in the brain. In the clinical sphere, we validated a gene therapy approach that led to significantly improved development and function of oligodendrocytes derived from the brains of mice modeling autism. This finding offers hope for developing genetic treatment for humans, which could improve the myelin production process in the brain. Furthermore, recognizing the significance of myelin impairment in autism—whether linked to the SHANK3 gene or not—opens new pathways for understanding the brain mechanisms underlying autism and paves the way for future treatment development”.

Does Looking Good Lead to Doing Good?

Written by Hilary on 25 November 2024. Posted in Newsroom.

New study finds that feeling attractive can lead to more generosity and kindness.

Does the global beauty trend have positive social aspects as well? A new study from Tel Aviv University shows that people who make an effort to improve their appearance—whether this effort is real or imagined, in the physical world or on social media—act more kindly towards others and are twice as likely to donate to charity.

The surprising study was led by Dr. Natalia Kononov, who completed her doctorate under the supervision of Prof. Danit Ein-Gar at the Coller School of Management at Tel Aviv University and is now a postdoctoral fellow at the Wharton School of Business at the University of Pennsylvania. The study, conducted in collaboration with Prof. Ein-Gar and Prof. Stefano Puntoni of Wharton, was published in the International Journal of Research in Marketing.

Prof. Danit Ein-Gar (Photo credit: Israel Hadari).

“When we enhance our appearance and feel beautiful—for example, after a fresh haircut—we behave in a more socially conscious manner”, explains Prof. Ein-Gar. “Why? Because we feel as though all eyes are on us, drawing attention, and so we strive to act better. It’s easy to criticize the selfie generation, constantly beautifying themselves and sharing polished photos, but we demonstrate a side effect of this behavior that can benefit society. People who feel good about their appearance can channel that feeling into good deeds”.

Dr. Natalia Kononov.

To test their hypothesis, the researchers conducted a series of experiments, some in virtual settings and others in a laboratory. In one lab experiment, participants were asked to use a filter to enhance a selfie they had taken. A control group, meanwhile, was asked to enhance a photo of an object in the room.

“The experimental group consisted of 50 participants, as did the control group”, Prof. Ein-Gar explains. “After viewing their enhanced photo, each participant collected an envelope with their payment in cash. Next to the payment envelope, there was a donation box so participants could voluntarily donate some or all of their payment. We observed that members of the experimental group, who saw themselves as more attractive, donated up to twice as much as those in the control group. It’s enough to imagine ourselves as more attractive—even just envisioning a more polished digital version of ourselves—to encourage prosocial behavior. This insight has significant practical implications. Until now, research has focused on the appearance of the donation seekers—whether the recipient or the fundraiser—and indeed, more attractive fundraisers have been found to raise more money. Our study introduces another relevant factor: the donor’s appearance. This opens the door to innovative strategies for streamlining charity campaigns, such as partnering with cosmetic companies, hairdressers, and beauty salons—for everyone’s benefit”.

Beauty and the Benefit

One of the most surprising experiments was conducted virtually, on Facebook. Clicking on a link randomly directed users to one of two “know yourself” questionnaires. The control group’s questionnaire asked about preferred architectural styles, while the experimental group’s questionnaire included questions about fashion styles and was designed to make respondents imagine themselves at their most attractive moments, such as envisioning themselves dressed up for a fancy social event. At the end of the questionnaire, a seemingly unrelated pop-up appeared with a link to a donation page. About 7% of respondents who answered the “beauty” questionnaire clicked on the donation link, compared to approximately 2% of those who answered the architectural questionnaire—a particularly impressive figure considering the average click-through rate on Facebook links is just 0.9%.

“Our society is obsessively focused on physical appearance while simultaneously criticizing this superficial behavior”, says Dr. Kononov. “People who are appearance-focused are often judged harshly, but we show that this behavior can have positive spillover effects that benefit others. Social mechanisms may evolve to create some balance, where behaviors that serve the individual are accompanied by byproducts that contribute to the greater good“.

Cotler Fellows Make a Difference

Written by Hilary on 25 November 2024. Posted in Newsroom.

TAU international students fight antisemitism globally

In the wake of October 7th and the ensuing war, Jewish communities around the world are experiencing a troubling surge in antisemitism, while Israelis find it increasingly difficult to advocate for the country on the international stage. One timely Tel Aviv University initiative, the Irwin Cotler Fellowship Program, is actively helping by providing key academic and practical knowledge to international students to counter anti-Jewish and anti-Israel sentiment in their home countries.

Since its inception, about 60 alumni of the program are now Israel’s goodwill ambassadors around the world, including students from Indonesia, Azerbaijan, Morocco, Turkey, Portugal, Nigeria, New Zealand, India, Belgium and more.

Each year, the program brings together 20 international students for weekly lectures and projects. They explore universal issues related to human rights and democracy; discuss Israeli society, history, diversity, and challenges; and attend field trips to communities and historical sites across the country. The Cotler Fellows is the flagship program of TAU’s Irwin Cotler Institute, founded in 2022 to advance instruction, training, and policy-oriented research on human rights, democracy, justice, and the fight against antisemitism and racism at large.

Says Prof. Uriya Shavit, Head of the Cotler Institute: “Fellows are exposed to a variety of viewpoints and encouraged to explore the issues independently and critically. We then
equip them with public speaking and grassroots organizational skills so that they can deliver workshops in their language to influential groups at home – such as the police, municipal leaders, sports coaches, and the like.”

Educating via Workshops

Indeed, Irwin Cotler Fellows are required to initiate, organize, and lead an international workshop, utilizing the knowledge and skills they gained in the program. Although the 2023-2024 academic year has been particularly complicated, that did not stop Cotler fellows from carrying out their missions. Ari Spielman, a 2024 Cotler Fellow from the United States who studied Environmental Studies at TAU, prepared a lecture about social movements in Israel following October 7th.

“I gave my presentation at my alma mater, SUNY Albany, in New York. I was worried about giving the talk initially. The University Student Union had just passed a BDS bill, the first in the SUNY system. Yet in the end, we still had a good turnout, with no issues. I felt very confident with how I was able to present the information and convey what has been occurring in Israel in an understandable way to the audience,” Spielman explains.

“My time as a Cotler fellow helped me improve my public speaking, and ability to efficiently share information. I am very grateful for having been given the opportunity to do the presentation,” he adds.

Some of the other Cotler Fellows’ workshops were conducted online and are posted on the Institute’s website and on YouTube. Here are a few examples:

Master student in Security & Diplomacy Julie Jakobsgaard (Denmark) – Antisemitism: Its Development and Present State in Denmark
Dental medicine student Joshua G. Cardenas (United States) – Balancing Tech Innovation & Ethics During Times of Crisis
Post-doc Dr. Mrinal Kashyap (India) – Israel-India Relations and Antisemitism Awareness
Law student Veronica Pana Igube (Nigeria) – Strategies for Combating Online Hate

Other workshops given by Fellows this year included: Anna Balogh (Hungary) on environmental peacebuilding and the Israeli-Palestinian conflict; Gülsen Aşam (Turkey) on the Syrian refugee crisis and the response of the Turkish government; Akman Sofuoğlu (Turkey) on Israel and misconceptions about the Israeli-Palestinian conflict; and Dacha Azelmad (Morocco) on preserving Jewish memory in Morocco.

“It has been an incredibly enriching experience for me. The insightful discussions and collaborative projects have broadened my understanding of key issues and made me closer to the Jewish culture and to Israel,” says Dacha Azelmad from Morocco, a 2024 Cotler Fellow who studied for an MA in Security and Diplomacy.

“I feel more equipped and inspired to contribute meaningfully to these important conversations in the future, and I am very grateful for this opportunity. Hopefully, my engagement does not stop here!” she adds.

Alumni in ActionBeyond the mandatory workshops, in the wake of the October 7 attack, graduates of the Cotler Fellowship program chose to not remain silent and used their new skills and knowledge to engage in pro-Israel action around the world.
In May 2024, 2023 Cotler Fellow Nathaniel Myking Udjus organized a support rally for Israel and against antisemitism in his hometown of Grimstad, Norway, together with several local political parties and political organizations. The rally drew over 500 participants from Southern Norway, who expressed their support for Israel and disagreement with the Norwegian government’s policies.

Nathaniel Myking Udjus speaking at an Israel support rally he organized in his hometown of Grimstad, Norway

Nathanial’s classmate Maia Bornsztein participated in numerous pro-Israel demonstrations that have been held in Argentina. Working with her colleagues, Maia has organized and participated in conferences on Israel and the war at local schools, universities, and more than twenty Jewish community institutions, as well as making online informative videos. Furthermore, as a member of the Latin American Jewish Congress, she has been very active in its social media campaigns, generating positive content about Jewish communities around the world and attending meetings with public officials to find common areas to build solidarity against antisemitism.

Other 2023 alumni similarly reached out. Rafael Nabizade moderated a webinar addressing how Israel and Azerbaijan are confronting Iranian-backed religious terrorism. Aryo Brahmantyo lobbied Indonesian media to cover the situation in a more balanced manner, providing video footage to raise awareness about the atrocities committed by Hamas.

Cotler Fellow Aryo Brahmantyo appearing on Indonesian television

Markus McCraith, Cotler Fellow in the 2024 cohort, initiated and helped organize a Cotler Institute ten-day series of seminars and public lectures in his home country of New Zealand. Senior members of the Jewish communities hailed the lectures and seminars as exceptionally empowering and informative and noted that the tour raised awareness among government agencies about the reality of antisemitism and helped establish new channels for communication and cooperation with the government.

“The Irwin Cotler Fellowship Program has truly been a once-in-a-lifetime experience for me,” McCraith says.

Justice, Justice Shall You Pursue

The Irwin Cotler Institute celebrates and advances the legacy of one of the greatest and most respected Canadian jurists and human rights champions in our time, Prof. Irwin Cotler, who is one of the lecturers at the Fellowship Program and also a TAU Governor and Honorary Doctor. “I hope that through our students we’ll create a critical mass of advocacy on behalf of the Jewish people and that Tel Aviv University will be at the forefront of that involvement,” he said at the Institute’s opening.

Hon. Irwin Cotler with wife Daniella at the TAU Canada Gala (photo: TAU Canada)

Prof. Cotler’s life and legacy were recently celebrated by our Tel Aviv University supporters in Montreal, Canada with 550 guests, family, and friends. “We paid tribute to an extraordinary person, who has dedicated his life and career to making the world a better place,” said the head of TAU Canada Montreal chapter Sharon J. Fraenkel, quoting former Canadian Supreme Court Justice Rosie Abella, who said, “We are all better people today because of Irwin”.

Nasal Spray Revolutionizes COVID Protection

Written by Hilary on 21 November 2024. Posted in Newsroom.

Researchers created an affordable, needle-free nasal spray COVID-19 vaccine.

A breakthrough in vaccine development: Prof. Ronit Satchi-Fainaro’s lab at TAU’s Faculty of Medical and Health Sciences collaborated with Professor Helena Florindo’s lab at the University of Lisbon to produce a novel nano-vaccine for COVID-19. The nano-vaccine, a 200-nanometer particle, trains the immune system against all common COVID-19 variants, just as effectively as existing vaccines. Moreover, unlike other vaccines, it is conveniently administered as a nasal spray and does not require a cold supply chain or ultra-cold storage. These unique features pave the way to vaccinating 3rd-world populations, as well as the development of simpler, more effective, and less expensive vaccines in the future. The revolutionary study was featured on the cover of the prestigious journal Advanced Science.

Prof. Ronit Satchi-Fainaro.

Prof. Satchi-Fainaro explains: “The new nano-vaccine’s development was inspired by a decade of research on cancer vaccines. When the COVID-19 pandemic began, we set a new goal: training our cancer platform to identify and target the coronavirus. Unlike Moderna and Pfizer, we did not rely on full protein expression via mRNA. Instead, using our computational bioinformatics tools, we identified two short and simple amino acid sequences in the virus’s protein, synthesized them, and encapsulated them in nanoparticles”. Eventually, this nano-vaccine proved effective against all major variants of COVID-19, including Beta, Delta, Omicron, etc.

“Our nano-vaccine offers a significant advantage over existing vaccines because it is needle-free and administered as a nasal spray,” notes Prof. Satchi-Fainaro. “This eliminates the need for skilled personnel such as nurses and technicians to administer injections, reducing contamination risks and sharp waste. Anyone can use a nasal spray, with no prior training”.

Room-Temperature Storage, Same Effectiveness

Another major advantage of the revolutionary nano-vaccine is its minimal storage requirements. Moderna’s sensitive mRNA-based vaccine must be kept at -20°C and Pfizer’s at -70°C, generating great logistic and technological challenges, such as shipping in special aircraft and ultra-cold storage – from the factory to the vaccination station. Prof. Satchi-Fainaro’s novel synthetic nanoparticles are far more durable and can be stored as a powder at room temperature. “There’s no need for freezing or special handling,” she says. “You just mix the powder with saline to create the spray. For testing purposes, as part of the EU’s ISIDORe (Integrated Services for Infectious Disease Outbreak Research feasibility program), we shipped the powder at room temperature to the INSERM infectious diseases lab in France. Their tests showed that our nano-vaccine is at least as effective as Pfizer’s vaccine”.

These important advantages—ease of nasal administration and regular storage and shipping — pave the way towards vaccinating at-risk populations in low-income countries and remote regions, which existing vaccines are unable to reach. Moreover, the novel platform opens the door for quickly synthesizing even more effective and affordable vaccines for future pandemics. “This is a plug-and-play technology,” explains Prof. Satchi-Fainaro. “It can train the immune system to fight cancer or infectious diseases like COVID-19. We are currently expanding its use to target a range of additional diseases, enabling the rapid development of relevant new vaccines when needed”.

The groundbreaking project has received competitive research grants from the Israel Innovation Authority and Merck under the Nofar program, as well as funding from Spain’s “La Caixa” Foundation Impulse as an accelerated program, and support from the ISIDORe feasibility program. It is also part of a broader vaccine platform development program at Professor Satchi-Fainaro’s lab, supported by a European Research Council (ERC) Advanced Grant.

Is There a Way to Stop Parkinson’s Disease at Its Source?

Written by Hilary on 14 November 2024. Posted in Newsroom.

TAU Researchers discovered a potential new target for developing effective treatments for Parkinson’s disease.

Researchers at Tel Aviv University discovered a new factor in the pathology of Parkinson’s disease, which in the future may serve as a target for developing new treatments for this terrible ailment, affecting close to 10 million people worldwide.

The researchers: “We found that a variant of the TMEM16F protein, caused by a genetic mutation, enhances the spread of Parkinson’s pathology through nerve cells in the brain”.

The study was led by Dr. Avraham Ashkenazi and PhD student Stav Cohen Adiv Mordechai from the Department of Cell and Developmental Biology at TAU’s Faculty of Medical and Health Sciences and the Sagol School of Neuroscience. Other contributors included: Dr. Orly Goldstein, Prof. Avi Orr-Urtreger, Prof. Tanya Gurevich and Prof. Nir Giladi from TAU’s Faculty of Medical and Health Sciences and the Tel Aviv Sourasky Medical Center, as well as other researchers from TAU and the University of Haifa. The study was backed by the Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease at TAU. The paper was published in the scientific journal Aging Cell.

Doctoral student Stav Cohen Adiv Mordechai explains: “A key mechanism of Parkinson’s disease is the aggregation in brain cells of the protein α-synuclein (in the form of Lewy bodies), eventually killing these cells. For many years, researchers have tried to discover how the pathological version of α-synuclein spreads through the brain, affecting one cell after another, and gradually destroying whole brain sections. Since α-synuclein needs to cross the cell membrane to spread, we focused on the protein TMEM16F, a regulator situated in the cell membrane, as a possible driver of this lethal process”.

α-synuclein spread in the mouse brain.

At first, the researchers genetically engineered a mouse model without the TMEM16F gene, and derived neurons from the brains of these mice for an in-vitro cellular model. Using a specially engineered virus, they caused these neurons to express the defective α-synuclein associated with Parkinson’s and compared the results with outcomes from normal brain cells containing TMEM16F. They found that when the TMEM16F gene had been deleted, the α-synuclein pathology spread to fewer healthy neighboring cells compared to the spread from normal cells. The results were validated in-vivo in a living mouse model of Parkinson’s disease.

TMEM16F Mutation Linked to Parkinson’s Risk in Ashkenazi Jews

In addition, in collaboration with the Neurological Institute at the Tel Aviv Sourasky Medical Center, the researchers looked for mutations (variants) in the TMEM16F gene that might increase the risk for Parkinson’s disease. Dr. Ashkenazi explains: “The incidence of Parkinson’s among Ashkenazi Jews is known to be relatively high, and the Institute conducts a vast ongoing genetic study on Ashkenazi Jews who carry genes increasing the risk for the disease. With their help, we were able to identify a specific TMEM16F mutation which is common in Ashkenazi Jews in general, and in Ashkenazi Parkinson’s patients in particular”. Cells carrying the mutation were found to secrete more pathological α-synuclein compared to cells with the normal gene. The researchers explain that the mechanism behind increased secretion has to do with the biological function of the TMEM16F protein: the mutation increases the activity of TMEM16F, thereby affecting membrane secretion processes.

Stav Cohen Adiv Mordechai: “In our study, we discovered a new factor underlying Parkinson’s disease: the protein TMEM16F, which mediates secretion of the pathological α-synuclein protein through the cell membrane to the cell environment. Picked up by healthy neurons nearby, the defective α-synuclein forms Lewy bodies inside them, and gradually spreads through the brain, damaging more and more brain cells. Our findings mark TMEM16F as a possible new target for the development of effective treatments for Parkinson’s disease. If, by inhibiting TMEM16F, we can stop or reduce the secretion of defective α-synuclein from brain cells, we may be able to slow down or even halt the spread of the disease through the brain”.

Dr. Ashkenazi emphasizes that research on the new Parkinson’s mechanism has only begun, and quite a number of questions still remain to be explored: Does inhibiting TMEM16F actually reduce the symptoms of Parkinson’s disease? Does the lipid composition of cell membranes play a part in spreading the disease in the brain? Is there a link between mutations in TMEM16F and the prevalence of Parkinson’s in the population? The research team intends to continue the investigation in these directions and more.

How Does the Brain Keep Calm?

Written by Hilary on 14 November 2024. Posted in Newsroom.

New Insight into Brain Stability: The Key Role of NMDA Receptors

Researchers at Tel Aviv University have made a fundamental discovery: the NMDA receptor (NMDAR)—long studied primarily for its role in learning and memory—also plays a crucial role in stabilizing brain activity. By setting the “baseline” level for activity in neural networks, the NMDAR helps maintain stable brain function amidst continuous environmental and physiological changes. This discovery may lead to innovative treatments for diseases linked to disrupted neural stability, such as depression, Alzheimer’s disease, and epilepsy.

The study was led by Dr. Antonella Ruggiero, Leore Heim, and Dr. Lee Susman from Prof. Inna Slutsky’s lab at the Faculty of Medical and Health Sciences at Tel Aviv University. Prof. Slutsky, who is also affiliated with the Sagol School of Neuroscience, heads the Israeli Society for Neuroscience and directs the Sieratzki Institute for Advances in Neuroscience. Additional researchers included Dr. Ilana Shapira, Dima Hreaky, and Maxim Katsenelson from the Faculty of Medical and Health Sciences at Tel Aviv University, and Prof. Kobi Rosenblum from the University of Haifa. The study was published in the prestigious journal Neuron.

“In recent decades, brain research has mainly focused on processes that allow information encoding, memory, and learning, based on changes in synaptic connections between nerve cells”, says Prof. Slutsky.

“But the brain’s fundamental stability, or homeostasis, is essential to support these processes. In our lab, we explore the mechanisms that maintain this stability, and in this study, we focused on the NMDAR—a receptor known to play a role in learning and memory”, Slutsky continues.

This comprehensive project used three primary research methods: electrophysiological recordings from neurons in both cultured cells (in vitro) and living, behaving mice (in vivo) within the hippocampus, combined with computational modeling (in silico). Each approach provided unique insights into how NMDARs contribute to stability in neural networks.

Dr. Antonella Ruggiero studied NMDAR function in cultured neurons using an innovative technique called “dual perturbation”, developed in Prof. Slutsky’s lab. “First, I exposed neurons to ketamine, a known NMDAR blocker”, she explains. “Typically, neuronal networks recover on their own after disruptions, with activity levels gradually returning to baseline due to active compensatory mechanisms. But when the NMDAR was blocked, activity levels stayed low and didn’t recover. Then, with the NMDAR still blocked, I introduced a second perturbation by blocking another receptor. This time, the activity dropped and recovered as expected, but to a new, lower baseline set by ketamine, not the original level”. This finding reveals the NMDAR as a critical factor in setting and maintaining the activity baseline in neuronal networks. It suggests that NMDAR blockers may impact behavior not only through synaptic plasticity but also by altering homeostatic set points.

Building on this discovery, Dr. Ruggiero sought to uncover the molecular mechanisms behind the NMDAR’s role in tuning the set point. She identified that NMDAR activity enables calcium ions to activate a signaling pathway called eEF2K-BDNF, previously linked to ketamine’s antidepressant effects.

How NMDARs Set the Brain’s Activity Baseline

Leore Heim investigated whether the NMDAR similarly affects baseline activity in the hippocampus of living animals. A major technical challenge was administering an NMDAR blocker directly to the hippocampus without affecting other brain areas, while recording long-term activity at the individual neuron level. “Previous studies often used injections that delivered NMDAR blockers across the entire brain, leading to variable and sometimes contradictory findings,” he explains. “To address this, I developed a method combining direct drug infusion into the hippocampus with long-term neural activity recording in the same region. This technique revealed a consistent decrease in hippocampal activity across states like wakefulness and sleep, with no compensatory recovery as seen with other drugs. This strongly supports that NMDARs set the activity baseline in hippocampal networks in living animals”.

Mathematician Dr. Lee Susman created computational models to answer a longstanding question: Is brain stability maintained at the level of the entire neural network, or does each neuron individually stabilize itself? “Based on the data from Antonella and Leore’s experiments, I found that stability is maintained at the network level, not within single neurons,” he explains. “Using models of neural networks, I showed that averaging activity across many neurons provides computational benefits, including noise reduction and enhanced signal propagation. However, we need to better understand the functional significance of single-neuron drift in future studies”.

Prof. Slutsky adds: “We know that ketamine blocks NMDARs, and in 2008, it was FDA-approved as a rapid-acting treatment for depression. Unlike typical antidepressants like Cipralex and Prozac, ketamine acts immediately by blocking NMDARs. However, until now, it wasn’t fully understood how the drug produced its antidepressant effects. Our findings suggest that ketamine’s actions may stem from this newly discovered role of NMDAR: reducing the activity baseline in overactive brain regions seen in depression, like the lateral habenula, without interfering with homeostatic processes. This discovery could reshape our understanding of depression and pave the way for developing innovative treatments”.

Eyes Wide Shut: Bats Can Navigate Long Distances Using Sound Alone

Written by Hilary on 12 November 2024. Posted in Newsroom.

Researchers found that bats can create a mental “sound map” of their environment.

A new study by Tel Aviv University and the Steinhardt Museum of Natural History has proven, for the first time, that bats can navigate in nature over many kilometers using only echolocation, without relying on other senses. The researchers explain: “It’s well-known that bats are equipped with a natural sonar, allowing them to emit sound waves that bounce back from nearby objects, helping them navigate. However, it’s also known that bats use their sense of sight during flight. Laboratory studies have shown that bats can navigate within enclosed spaces using only echolocation — but sonar ‘sees’ only about 10 meters ahead, so what happens under natural conditions, in open areas stretching over many kilometers? Can bats rely solely on echolocation for long-distance navigation?” In this study, that question was explored in depth for the first time.

They Follow the Echo

The research was led by Prof. Yossi Yovel of Tel Aviv University’s School of Zoology, Sagol School of Neuroscience, and Steinhardt Museum of Natural History, along with Dr. Aya Goldshtein, formerly a doctoral student of Prof. Yovel and currently a researcher at the Max Planck Institute in Germany. Additional partners from Tel Aviv University included Prof. Sivan Toledo of the Blavatnik School of Computer Science; Xing Chen, Dr. Eran Amichai, and Dr. Arjan Boonman of the School of Zoology; and Lee Harten of the Sagol School of Neuroscience. Prof. Ran Nathan and Dr. Yotam Orchan of the Hebrew University and Prof. Iain Couzin of the Max Planck Institute in Germany also participated in the study, which was published in the journal Science.

The innovative research carried out over six years, utilized a unique tracking system installed in Israel’s Hula Valley. Using this GPS-like technology, the researchers could track the flight of tiny bats from the species known as Kuhl’s pipistrelle, each weighing only six grams —— the smallest mammal ever to be monitored in this way.

For the study, the researchers collected around 60 bats from their roost in the Hula Valley area and moved them about three kilometers away from the roost — still within their familiar habitat. A tag was attached to each bat, and the eyes of some were covered with a cloth strip, temporarily preventing them from seeing during flight, though they could remove the covering with their feet upon landing. In addition, the researchers employed techniques to temporarily disrupt the bats’ sense of smell and magnetic sense, thereby creating conditions in which they would be able to find their way home using only echolocation. Remarkably, the bats managed to return to their roost without difficulty.

In the second phase, the researchers built a computerized acoustic model of the bats’ natural environment in the Hula Valley. Prof. Yovel explains: “This model is based on a 3D map of the area where the bats navigate, reflecting the echoes that the bat hears as it uses echolocation to journey through its surroundings. In examining the bats’ flight paths, we discovered that they choose routes where the echoes contain a lot of information, which helps them navigate. For example, an area rich in vegetation, such as bushes and trees, returns echoes with more information than an open field, making bats less likely to fly over open terrain. We also found that some areas are characterized by distinct echoes, which are picked up by the bats. These findings strengthened our hypothesis that in any given area, bats know where they are based on the echoes. The bats effectively create an acoustic map in their head of their familiar environment, which includes a variety of active ‘sound landmarks’ (echoes) — just as every sighted person has a visual map of their everyday surroundings”.

פרופ' יוסי יובל

Hyperbaric Oxygen Therapy: A Promising Treatment for PTSD Symptoms

Written by Hilary on 11 November 2024. Posted in Newsroom.

Biological damage in PTSD sufferers can be treated with a specialized protocol.

Researchers at Tel Aviv University and the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center have demonstrated that hyperbaric oxygen therapy (HBOT) improves the condition of PTSD sufferers who have not responded to psychotherapy or psychiatric medications. The researchers: “Our unique therapeutic protocol affects the biological brain ‘wound’ associated with PTSD, and effectively reduces typical symptoms such as flashbacks, hypervigilance, and irritability. We believe that our findings give new hope to millions of PTSD sufferers and their families, all over the world”.

The study was led by Prof. Shai Efrati and Dr. Keren Doenyas-Barak from the Faculty of Medical and Health Sciences at Tel Aviv University and the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center. Other contributors include Dr. Ilan Kutz, Gabriela Levi, Dr. Erez Lang, Dr. Amir Asulin, Dr. Amir Hadanny, and Dr. Ilia Beberashvili from the Shamir Medical Center, and Dr. Kristoffer Aberg and Dr. Avi Mayo from the Weizmann Institute. The paper was published in The Journal of Clinical Psychiatry.

“At present, we treat hundreds of PTSD sufferers every day”

Prof. Efrati: “Due to our unfortunate circumstances, Israel has become a global leader in the field of PTSD. Before the Hamas attack on Oct. 7, 2023, approximately 6,000 IDF veterans had been recognized as PTSD sufferers, with many others, both soldiers and citizens, not yet acknowledged by the authorities. Following Oct. 7 and the ensuing war, these numbers have risen sharply. Tens of thousands of soldiers, and much larger numbers of civilians, are likely to be diagnosed with PTSD. The world-leading Sagol Center for Hyperbaric Medicine, the largest of its kind in the world, is rising to the challenge – with a comprehensive therapeutic array comprising hyperbaric facilities combined with diverse mental health professionals, psychologists and psychiatrists. At present, we treat hundreds of PTSD sufferers every day, aiming to reach one thousand patients per year”.

Dr. Doenyas-Barak: “PTSD (Post-Traumatic Stress Disorder) is defined as the mental outcome of exposure to a life-threatening event. About 20% of those who have undergone such an experience will develop PTSD, which can lead to substantial social, behavioral, and occupational dysfunctions. In extreme cases, the disorder can severely impact their quality of life, family life, and professional performance. Symptoms include a range of emotional and cognitive changes, nightmares and flashbacks, hypervigilance, irritability, and avoidance – so as not to trigger traumatic experiences. In many cases, PTSD is resistant to psychotherapy and common psychiatric medications. Past studies on therapy-resistant sufferers have found changes in the structure and function of brain tissues, or a ‘biological wound’ that explains such treatment resistance. In our study, we wanted to determine whether hyperbaric therapy can help these patients”.

Testing HBOT for PTSD Relief

The study, which began in 2019 and ended in the summer of 2023, included 98 male IDF veterans diagnosed with combat-associated PTSD, who had not responded to either psychotherapy or psychiatric medications. Participants were divided into two groups: one group received HBOT treatment, breathing pure high-pressure oxygen, while the other underwent the same procedure, but received a placebo treatment, breathing regular air. 28 members of each group completed the process and the following evaluation.

Dr. Doenyas-Barak: “The HBOT was administered in accordance with a unique treatment protocol developed at our Center. Every patient is given a series of 60 two-hour treatments in our hyperbaric chamber, during which they are exposed to pure 100% oxygen at a pressure of 2 atmospheres (twice the normal air pressure at sea level). Our protocol specifies alternately breathing oxygen and regular air: every 20 minutes the patient removes the oxygen mask and breathes regular air for five minutes. The drop in oxygen level, at the tissue level, activates healing processes and thus enhances the therapeutic effect”.

Functional MRI before and after HBOT. Photo credit: The Shamir Medical Center.

The results were encouraging, with improvements observed both at the clinical level and in fMRI imaging. The group that received hyperbaric therapy showed improved connectivity in brain networks, alongside a decline in all typical PTSD symptoms. In the placebo group, on the other hand, no change was observed in either the brain or clinical symptoms. Prof. Efrati: “Our study demonstrated that HBOT induces biological healing in the brain of PTSD sufferers. Curing the biological wound also impacts clinical symptoms. We believe that HBOT, based on the special protocol we have developed, can bring relief to numerous PTSD sufferers worldwide, allowing them to resume a normative life in their community and family”.

Prof. Efrati emphasizes:

“Patients suffering from PTSD should undergo HBOT only at professional hyperbaric centers, where treatment is delivered by multidisciplinary teams experienced in trauma care. Unsupervised, private hyperbaric chambers are unable to provide a proven, effective protocol. Additionally, patients must receive a thorough professional evaluation to ensure they are suitable for HBOT and to determine what additional support is needed throughout their treatment journey”.

Israel’s Ministry of Defense funds HBOT for veterans who need it.

Buzzed but Never Tipsy: Hornets’ Remarkable Alcohol Tolerance

Written by Hilary on 10 November 2024. Posted in Newsroom.

Oriental hornets are the only animals able to drink unlimited amounts of alcohol.

A new study from the School of Zoology and the Steinhardt Museum of Natural History at Tel Aviv University has revealed that the Oriental hornet is the only known animal capable of chronically consuming alcohol in high concentrations with almost no negative effects on its health or lifespan. The research team says, “This is a remarkable animal that shows no signs of intoxication or illness even after ingesting huge amounts of alcohol.”

The research was conducted under the leadership of postdoctoral fellow Dr. Sofia Bouchebti from Prof. Eran Levin’s laboratory at Tel Aviv University’s School of Zoology and the Steinhardt Museum of Natural History. The study was published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The researchers explain that alcohol is commonly produced in nature through the breakdown of sugars by yeasts and bacteria, primarily found in ripe fruits and nectar. Although alcohol contains nearly twice the amount of energy as sugar, it is toxic to most animals — including us humans — with occasional consumption, and especially with chronic use. Among the animals known to consume alcohol are fruit flies, which show signs of alcohol poisoning even at relatively low concentrations, and treeshrews — mammals native to East Asia that feed on ripe, alcohol-rich fruits — who show symptoms such as fatty liver and other effects indicative of alcoholism after consuming low concentrations of alcohol continuously for several days.

As for humans, many of us like consuming alcohol. Humans domesticated the wine grape around 10,000 years ago, and compared to other animals, we can tolerate and often enjoy consuming relatively high amounts of alcohol. However, as we know, alcohol has significant effects on behavior, cognition, and, of course, health, with a host of diseases linked to its consumption.

Hornets Can Handle Their Liquor

In the new study, the research team tested the Oriental hornet’s ability to consume alcohol and break it down. Dr. Bouchebti explains: “The hornets naturally store yeasts in their digestive system, which provides them with a unique environment that allows the yeast to develop and reproduce, creating new strains. One explanation is that hornets transfer yeasts to fruits, which indirectly contributes to the production of wine. In our study, we labeled the alcohol consumed by the hornets with a heavy carbon isotope. As the alcohol is metabolized, it breaks down into carbon dioxide, which is exhaled. By measuring the amount of labeled carbon dioxide emitted, we were able to estimate the speed at which the alcohol was broken down. The findings were surprising; we were amazed to see the rapid rate at which the hornets metabolized the alcohol”.

In the next stage, the researchers sought to determine whether the Oriental hornet ever becomes intoxicated. Does increased alcohol consumption affect their behavior, for example causing aggression or impacting their nest-building abilities? Here too, the findings were surprising: even when consuming high concentrations of alcohol (80 percent alcohol as the sole source of nutrition) there was no noticeable effect on the hornets’ behavior. In the final phase of the study, the researchers tested whether alcohol had any impact on the hornets’ lifespan and health. Once again, they were amazed to discover that no differences were found between the lifespan of hornets that consumed only alcohol for their entire lives (three months) and hornets that consumed sugar water.

No Hangovers Here

Prof. Levin concludes: “To the best of our knowledge, Oriental hornets are the only animal adapted to consuming alcohol as a metabolic fuel. They show no signs of intoxication or illness, even after chronically consuming huge amounts of alcohol, and they eliminate it from their bodies very quickly. In a bioinformatics analysis of the Oriental hornet’s genome, conducted by Prof. Dorothee Huchon, it was discovered that the hornet possesses several copies of the gene responsible for producing the enzyme that breaks down alcohol; this genetic adaptation may be related to their incredible ability to handle alcohol. We propose that the ancient relationship between hornets and yeast led to the development of this adaptation. Furthermore, while alcohol-related research is highly advanced, with 5.3 percent of deaths in the world linked to alcohol consumption, we believe that, following our research, Oriental hornets could potentially be used to develop new models for studying alcoholism and the metabolism of alcohol”.

Chemistry Researchers Awarded Prestigious ERC Synergy Grant

Written by Hilary on 5 November 2024. Posted in Newsroom.

The European Research Council (ERC) has announced the results of the 2024 ERC Synergy Grant Call. Among the funded projects is an international collaboration, coordinated by Tel Aviv University researchers and titled “Unravelling the Mysteries of Vibrational Strong Coupling” (UNMYST). The prestigious ERC Synergy grants are awarded to leading researchers in their fields across all areas of science, and it is intended to promote groundbreaking interdisciplinary research.

The UNMYST project is an international collaboration between leading experimental and theoretical groups, including Dr. Tal Schwartz and Prof. Sharly Fleisher from the School of Chemistry at Tel Aviv University, Prof. Abraham Nitzan, an emeritus of the School of Chemistry at Tel Aviv University and a Donner Professor of Physical Sciences in University of Pennsylvania, Prof. Thomas Ebbesen and Cyriaque Genet from the University of Strasbourg, France, Prof. Angel Rubio and Dr. Michael Ruggenthaler from the Max Planck Institute for the Structure and Dynamics of Matter, Germany, and Dr. Dominik Sidler from the Paul Scherrer Institute in Switzerland.

According to the project coordinator Dr. Tal Schwartz, the UNMYST project will explore how tailoring the electromagnetic environment influences chemical and physical processes in molecular systems in the so-called “strong light-matter coupling” regime. The researchers anticipate that the results of the project will establish fundamental insights into such novel phenomena, which will lead to future breakthroughs with far-reaching implications for chemistry and materials sciences.

Author: Hilary

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