In mice with active inflammation, suppressing the neurons that remembered it produced an immediate reduction in the inflammation.

Your phone pings. It’s a message from a friend you met for drinks last night, who just tested positive for Covid-19.

Your throat starts feeling scratchy. A short cough sputters out. Is your body temperature rising? You run to take a PCR test. When the results come back negative, you realize it was all in your head — a psychosomatic response.

Researchers from the Technion – Israel Institute of Technology in Haifa wanted to explore the connection between the brain’s perception of illness and the real thing.

They induced inflammation in mice, and after the inflammation subsided, the researchers triggered the neurons in the mice’s brains that were active during the initial inflammation.

The result was dramatic: The inflammation re-emerged in the same area as before. Simply “remembering” the inflammation was enough to reactivate it.

The researchers then wondered: If the brain can generate disease, can the brain also turn it off?

The answer was a resounding yes. In mice with active inflammation, suppressing the neurons that remembered it produced an immediate reduction in the inflammation.

There’s no guarantee this experiment would work in human beings. But it raises the possibility of a new therapeutic avenue for treating chronic inflammatory conditions such as Crohn’s disease and psoriasis.

The brain’s ability to bring on illness psychosomatically is more a feature than a bug, explained Prof. Asya Rolls, of the Technion’s Faculty of Medicine.

“The body needs to respond to infection as quickly as possible before the attacking bacteria or viruses can multiply,” she said.

“If certain activity – for example consuming particular foods – has exposed the body to infection and inflammation once, there is an advantage to gearing up for battle when one is about to engage in the same activity again. A shorter response time would allow the body to defeat the infection faster and with less effort.”

The research was led by Tamar Koren, an MD-PhD student in Rolls’ lab. Other participants included Dr. Kobi Rosenblum of the University of Haifa and Dr. Fahed Hakim of EMMS Hospital in Nazareth.

The study was supported by the European Research Council (ERC) Starting Grant, the Allen and Jewel Prince Center for Neurodegenerative Disorders of the Brain, the Howard Hughes Medical Institute (HHMI) and the Wellcome Trust.

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Can our brain make our body sick? Likely yes, Israeli research shows

Technion scientists uncovered how neurons can trigger physiological responses in the body that translate in real illnesses but might also help treat them.

Can our brain trigger an actual illness in the body? New research by Technion-Israel Institute of Technology scientists conducted on mice suggests that the answer is likely yes.

Over the years, the intuitive idea that the brain exercises a significant influence on people’s physical well-being has been supported by increasing scientific evidence.

“Several years ago, we studied the mechanism behind the placebo effect, demonstrating that when people experience a positive expectation, their conditions improve in many ways,” Technion Prof. Asya Rolls said.

“We were able to show that by activating brain areas that are related to positive expectations, we would boost the immune response,” she said. “What amazed us was how precise this response was, and therefore we thought that the brain could not have such an exact control of the system without knowing what its status is.”

The researchers started to examine whether the brain is able to represent the status of the immune system.

The new study was led by Rolls and her MD/PhD student Tamar Koren and was conducted in cooperation with Dr. Kobi Rosenblum of the University of Haifa and Dr. Fahed Hakim of EMMS Nazareth Hospital. The results were published in the journal Cell on Monday.

The scientists checked which areas of the brain would be activated when mice experienced genetically induced colon inflammation. Among others, the insular cortex – which is responsible for sensations such as thirst, hunger and pain and other manifestations of the body’s physiological state – presented increased neurological activity.

“When we reactivated the same neurons afterward, we recorded the same inflammatory response,” Rolls said. “It was quite shocking.”

The results offer evidence that the brain contains a representation of the immune system, and it can reactivate it when presented with specific stimuli and possibly other forms of memories, the researchers said.

The brain does not cause the body to be reinfected by a pathogen, but it might potentially trigger a reaction in the body similar to the one caused by the original infection, they said.

“We have to remember that, many times, the damage to the body is not caused by the pathogen itself but, rather, by the immune system’s reaction to it,” Rolls said.

The mechanism may help explain what triggers psychosomatic disorders, which are health problems that appear without any apparent biological cause, the researchers found. Autoimmune diseases or other conditions, such as Crohn’s disease, could also be based on a similar process.

It would be wrong to assume that the results obtained from the study on mice will translate in humans in the exact same way, Rolls said.

However, there is hope that the research can contribute to understanding better how certain diseases work and how to treat them, possibly by inhibiting the neurons from activating and triggering the inflammation.

“There are many ways we can control neuronal activities in the human brain, for example, through magnetic or electrical stimulation or by neurofeedback when a person learns how to control their neurons on their own,” Rolls said.

“We know that we can do it because we know the power of a psychosomatic effect,” she said. “For example, during the clinical trial of the COVID vaccine, many people who received the placebo experienced very similar side effects to those who received the actual vaccine. Clearly, this was caused by some mental process resulting in a physiological response.”

Israeli scientists from the Technion – Israel Institute of Technology have developed an artificial molecule that could inhibit the development of Alzheimer’s disease, conceivably paving the way for better treatment of the disease.

The Technion scientists collaborated with The French National Centre for Scientific Research (CRNS) and published their findings in the weekly peer-reviewed Angewandte Chemie scientific journal published on behalf of the German Chemical Society.

The study was led by Professor Galia Maayan and doctoral student Anastasia Behar from the Schulich Faculty of Chemistry at the Technion, in collaboration with Prof. Christelle Hureau from the Laboratoire de Chimie de Coordination du CNRS, Toulouse, France.

The findings showed that an accumulation of copper ions, when interacting with the amyloid beta (Aβ) can lead to cell toxicity, causing dangerous conditions, including degenerative diseases of the brain, like Alzheimer’s. This accumulation of copper disrupts the removal of the Aβ , a peptide linked to the plaques that form in the brains of Alzheimer’s patients.

A 2013 study appearing in the Proceedings of the National Academy of Sciences journal written by a group led by Rashid Deane, a research professor in the University of Rochester’s Medical Center department of neurosurgery, said that copper accumulation in the body increases the progression of Alzheimer’s disease by preventing toxic proteins from leaving the brain. More specifically, copper ion interaction with the Aβ promotes ROS, or reactive oxygen species, highly reactive chemicals formed from oxygen. The production of ROS due to metal ions, like copper, leads to oxidative damages to the Aβ peptide and the potential formation of amyloid plaque.

Researchers have learned that the breakdown of the copper- Aβ complex and the removal of copper from the amyloid, prevents cells’ death and inhibition of the disease. The extraction of copper is done by a process called chelation or using molecules that bind the copper ions and extract them from the amyloid.

Developing the foundation

Technion Chemistry Professor Galia Maayan did not begin her career by studying copper ion accumulation and its impact on degenerative diseases. Instead, she simply focused on the molecule.

“I’m a chemist. So I look at a molecule and I said, ‘Oh I have this molecule, I have this metal ion, in this case, copper, how can I design something that is selective for copper?’ And then I will think about other applications,” she tells NoCamels, “When I did my postdoc at NYU, I learned a lot about these peptide mimics or peptoids. I developed chelators that are not selective [to specific metal ions.]”

Prof. Maayan developed the foundation for copper and zinc-binding of peptoids and investigated how peptoids bound them — something she says no one had ever done up to that point — but it wasn’t until she met her first PhD student, Maria Baskin, (another author of the paper), that she understood that the molecules could be good for chelating metal ions related to specific diseases.

“We discussed copper, and then we started to think about Alzheimer’s,” she says, “and then we started to work on it.”

Prof. Maayan and Baskin developed the first generation of chelator molecules selective to copper. But they were not water soluble, she explains. “In order to start making the drugs you want to develop, you need your molecule to be, at least to a certain extent, water soluble.”

The Technion researchers developed their own method of making the molecule water soluble, without changing its shape or organization and patented the result. Thus, a water soluble peptoid chelator was created that could still selectively bind copper. Meanwhile, Anastasia Behar, who joined Prof. Maayan’s lab while completing her Master’s in Chemistry at the Technion, was sent to France for three months to work with CRNS after Prof. Maayan made a connection with Prof. Christelle Hureau.

Behar tells NoCamels that in France, the researchers created targeted environments where they could simulate processes in the brain where the accumulation of metals bound to Aβ was happening.

“Then we added our molecule and tested if it can interact with the amyloid-beta, take out the copper, and stop the radical production, which the molecule did eventually,” she explains.

“While working on the molecule, Nastia [Anastasia] learned how to do biochemical experiments to show the biology that the molecule can do. All of the things that we think can lead us toward future development of peptoids as drugs for Alzheimer’s,” Prof. Maayan said.

The Technion researchers developed their own method of making the molecule water soluble, without changing its scaffold or the way it was organized. This was tested in France. The water soluble peptoid chelator, a synthetic molecule dubbed P3, was able to perform its task selectively. It strongly binds copper and forms CuP3, extracting the copper from the amyloid. By doing this, it inhibits and even suppresses the formation of harmful oxidizing agents, without creating new processes, which neutralize amyloid toxicity.

Prof. Maayan says it’s important to note that the molecule that the researchers established is not the actual molecule they would like to be used when creating drug treatments for Alzheimer’s.

“It has solubility issues, stability issues. This is not a molecule we’re going to develop. This is just a base,” she tells NoCamels, “We are going to take it further and develop more and more molecules that will be better. Right now we’ve just put down the foundation and this is the breakthrough. We will make molecules that are more feasible later on.”

The next step, Prof. Maayan explains, is to go beyond the mimicking of an environment of a cell or of the brain in terms of a PH solution and to do more in-vitro experiments, or experiments with cells.

“We’ll do some in vitro experiments, then we will optimize the chemistry again, and then go back to in vitro until we are ready to go in vivo [with a living organism.],” she says, “It’s a long process. It can take several years, but we see the way so it’s not vague. We see the way and we now know what we need to do.”

Since the new algorithm was introduced, Maccabi health fund doctors have treated tens of thousands of UTI cases, and there has been a drop of around 35% in the need to switch antibiotics following the development of bacterial resistance to the drug prescribed.

Doctors at Israel’s Maccabi national health fund have recently begun working with an Artificial Intelligence-based predictive algorithm that advises doctors in the process of deciding on personalized antibiotic treatment for patients.

The new algorithm was developed by the Technion – Israel Institute of Technology together with KSM (Kahn-Sagol-Maccabi), the Maccabi Research and Innovation Center.

Maccabi chose to focus its first diagnoses on urinary tract infection – the most common bacterial infection among women. Around 30% of females suffer from the infection at least once during their lifetime, and up to 10% experience recurrent infections. Until now, in most cases, general treatment has been administered based on clinical guidelines and medical judgment. Sometimes, the bacteria prove to be antibiotic-resistant, resulting in the need to change the treatment plan.

Since the new algorithm was introduced, Maccabi doctors have treated tens of thousands of cases, and there has been a drop of around 35% in the need to switch antibiotics following the development of bacterial resistance to the drug prescribed.

This is significant because accuracy in the choice of antibiotics is far greater thanks to the new technology. In light of the success of this new development in the treatment of UTI, Maccabi has begun working on the development of additional detection systems that will help to contend with other infectious diseases that require personalized treatment with antibiotics.

The automated system works by recommending the most suitable antibiotic treatment for the patient to the doctor, based on clinical guidelines and other criteria such as age, gender, pregnancy status, residence in an assisted living facility, and personal history of UTI and antibiotics administered.

The unique algorithm was developed by Prof. Roy Kishony and Dr. Idan Yelin of the Technion Faculty of Biology, in cooperation with KSM, headed by Dr. Tal Patalon, and was introduced and implemented among Maccabi’s doctors by the health fund’s Medical Informatics team and Chief Physician’s Department.

“The algorithm we developed together with Maccabi’s experts is a major milestone in personalized medicine on the way to AI-based antibiotic treatments, which are personally tailored to the patient according to the prediction of treatment response and mitigate the development of resistant bacteria,” said Kishony.

Dr. Shira Greenfield, Director of Medical Informatics at Maccabi, said: “The significance of administering personalized antibiotic treatment is that it lowers the risk of antibiotic resistance developing – a global problem which all healthcare entities are working to solve.”