Genetics Influence Level of Depression Tied to Trauma Exposure, Study Finds – GenomeWeb

October 3, 2022 medical

Genetics can influence the development of major depressive disorder (MDD) in affected individuals who were previously exposed to trauma, according to new study appearing in JAMA Psychiatry this week. Self-reported trauma exposure, particularly that occurring in childhood, has an established role in depression, and research has indicated that higher levels of trauma are linked to MDD. However, the interplay between genetics and trauma on depression has not been fully explored. In their new paper, researchers from the University of Edinburgh analyzed genomic and other data on roughly 150,000 adult participants in the UK Biobank who showed depressive symptoms and/or neuroticism and reported exposure to a range of different traumas. They find that genome-by-trauma exposure interactions can explain up to 20 percent of variation in MDD and more often in males versus females. The study results, the authors write, suggest that "exploring mechanisms underlying genome-by-trauma exposure interactions may be useful in identifying at-risk individuals and intervention targets ... [and] may provide explanations for depression prevalence differences across the different sexes."

Genetics

Howard University’s Office of Research Awarded $11.5 Million From Chan Zuckerberg Initiative To Advance Genomics And Genetics Research – The Dig

October 3, 2022 medical

WASHINGTON Today, the Chan Zuckerberg Initiative (CZI) announced a partnership with Howard Universityand the nations three other historically Black medical colleges to further support cutting-edge scientific research to address significant gaps in genomics. CZIs Accelerate Precision Health (APH) program will award $11.5 million to Howard University's Office of Research over five years, allowing the University to expand research in the genome field, bring on renowned faculty, fund post-doctoral fellows, and support grant writing for future initiatives.

The $11.5 million award represents the latest stride toward fulfilling a key research goal outlined in the Howard Forward Office of Research strategic plan to leverage Howards genetic research to attract and mobilize resources to tackle global challenges, especially as they relate to Black populations. Black communities have been historically underrepresented in clinical trials and genetics research and today are still often excluded from medical studies. Recently, during the COVID-19 pandemic, despite Black Americans suffering a higher mortality rate than whites, many studies excluded Black participants.

To me, genetics research is more than just an academic pursuit, said Howard University President Wayne A. I. Frederick, M.D., MBA. As someone with sickle cell anemia, the study of genetics is not abstract. When I was born, people with sickle cell disease were told that they would not live beyond childhood. Today, a child born with sickle cell disease has somewhere around a 99% chance of living to adulthood. Those advances didnt happen by accident: Howard researchers have participated in every clinical trial that has led to FDA-approved medications for sickle cell disease treatment. This grant from CZI will allow us to continue to break new ground in genetics and genomics research for generations to come.

I am incredibly excited for this new venture with CZI to expand Howards important work in the fields of genomics and genetics, said Bruce Jones, Ph.D., Vice President for Research at Howard University. Research partnerships at Howard expand our understanding of issues impacting the Black community, from genetics and genomics and other STEM fields, to groundbreaking research in literature, the arts, law and other social science fields, leading to advancements in policy, medicine, and culture that benefit all communities.

For generations, Howard University has been at the forefront of genomics and genetics research, with a focus on the Black community. More than 50 years ago, Howard launched the Center for Sickle Cell Disease with the goal of providing care for patients and advancing research into sickle cell disease, the most frequent rare genetic disease, which mostly affects people of African descent. Twenty years ago, Howard launched the first large-scale collection of genetic profiles of African Americans.

Today, researchers at the National Human Genome Center at Howard University continue to work on the frontlines of genomics and genetics, including research by Dr. Angel Byrd on gene expression of Alibert Bazin syndrome and other lymphomas that disproportionately harm Black patients and Dr. Bernard Kwabi-Addos genetic research of prostate cancer disparities in Black communities.

The Howard University Accelerating Precision Health grant is led by co-principal investigators Kera Lawson, Ph.D., executive director of research development, and Pamela A.G. Clarke, MSc., director of research development in the Office of Research.

Specific initiatives at Howard to be funded by the CZI APH program include:

The new partnership will create new opportunities for cross-collaboration between Chan Zuckerberg Initiative staff and Howard faculty and students, including: the matching of Howard faculty expertise with other CZI research partners to foster joint interdisciplinary efforts and research; CZI professional development and training opportunities for Howard faculty; and opportunities for Howard students to learn new techniques outside of their home institution.

Pictured:Howard University'sDr. Marjorie C. Gondr-Lewis and team,whose NeuroPsychoPharmacology Laboratoryconductsprecision brain health research. Photo image courtesy of CZI.

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About Howard University

Founded in 1867, Howard University is a private, research university that is comprised of 14 schools and colleges. Students pursue more than 140 programs of study leading to undergraduate, graduate and professional degrees. The University operates with a commitment to Excellence in Truth and Service and has produced one Schwarzman Scholar, three Marshall Scholars, four Rhodes Scholars, 12 Truman Scholars, 25 Pickering Fellows and more than 165 Fulbright recipients. Howard also produces more on-campus African American Ph.D. recipients than any other university in the United States. For more information on Howard University, visit http://www.howard.edu.

About the Chan Zuckerberg Initiative

The Chan Zuckerberg Initiative was founded in 2015 to help solve some of societys toughestchallengesfrom eradicating disease and improving education, to addressing the needs of ourcommunities. Through collaboration, providing resources and building technology, our mission is to help build a more inclusive, just, and healthy future for everyone. For more information, please visit http://www.chanzuckerberg.com.

Media contact: Sholnn Freeman; sholnn.freeman@howard.edu

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Howard University's Office of Research Awarded $11.5 Million From Chan Zuckerberg Initiative To Advance Genomics And Genetics Research - The Dig

Genetics

CIA Just Invested In Woolly Mammoth Resurrection Tech – The Intercept

October 3, 2022 medical

As a rapidly advancing climate emergency turns the planet ever hotter, the Dallas-based biotechnology company Colossal Biosciences has a vision: To see the Woolly Mammoth thunder upon the tundra once again. Founders George Church and Ben Lamm have already racked up an impressive list of high-profile funders and investors, including Peter Thiel, Tony Robbins, Paris Hilton, Winklevoss Capital and, according to the public portfolio its venture capital arm released this month, the CIA.

Colossal says it hopes to use advanced genetic sequencing to resurrect two extinct mammals not just the giant, ice age mammoth, but also a mid-sized marsupial known as the thylacine, or Tasmanian tiger, that died out less than a century ago. On its website, the company vows: Combining the science of genetics with the business of discovery, we endeavor to jumpstart natures ancestral heartbeat.

In-Q-Tel, its new investor, is registered as a nonprofit venture capital firm funded by the CIA. On its surface, the group funds technology startups with the potential to safeguard national security. In addition to its long-standing pursuit of intelligence and weapons technologies, the CIA outfit has lately displayed an increased interest in biotechnology and particularly DNA sequencing.

Why the interest in a company like Colossal, which was founded with a mission to de-extinct the wooly mammoth and other species? reads an In-Q-Tel blog post published on September 22. Strategically, its less about the mammoths and more about the capability.

Biotechnology and the broader bioeconomy are critical for humanity to further develop. It is important for all facets of our government to develop them and have an understanding of what is possible, Colossal co-founder Ben Lammwrote in an email to The Intercept. (A spokesperson for Lamm stressed that while Thiel provided Church with$100,000 in funding to launchthe woolly mammoth project that became Colossal, he is not a stakeholderlike Robbins, Hilton, Winklevoss Capital, and In-Q-Tel.)

Colossal uses CRISPR gene editing, a method of genetic engineering based on a naturally occurring type of DNA sequence. CRISPR sequences present on their own in some bacterial cells and act as an immune defense system, allowing the cellto detect and excise viral material thattries to invade. The eponymous gene editing technique was developed to function the same way, allowing users to snip unwanted genes and program a more ideal version of the genetic code.

CRISPR is the use of genetic scissors, Robert Klitzman, a bioethicist at Columbia University and a prominent voice of caution on genetic engineering, told The Intercept. Youre going into DNA, which is a 3-billion-molecule-long chain, and clipping some of it out and replacing it. You can clip out bad mutations and put in good genes, but these editing scissors can also take out too much.

The embrace of this technology, according to In-Q-Tels blog post, will help allow U.S. government agencies to read, write, and edit genetic material, and, importantly, tosteerglobal biological phenomena that impact nation-to-nation competition whileenabling the United States to help set the ethical, as well as the technological, standards for its use.

In-Q-Tel did not respond to The Intercepts requests for comment.

In recent years, the venture firms portfolio has expanded to include Ginkgo Bioworks, a bioengineering startup focused on manufacturing bacteria for biofuel and other industrial uses; Claremont BioSolutions, a firm that produces DNA sequencing hardware; Biomatrica and T2 Biosystems, two manufacturers for DNA testing components; and Metabiota, an infectious disease mapping and risk analysis database powered by artificial intelligence. As The Intercept reported in 2016, In-Q-Tel also invested in Clearista, a skincare brand that removes a thin outer epidermal layer to reveal a fresher face beneath it and allow DNA collection from the skin cells scraped off.

President Joe Bidens administration signaled its prioritization of related advances earlier this month, when Biden signed an executive order on biotechnology and biomanufacturing. The order includes directives to spur public-private collaboration, bolster biological risk management, expand bioenergy-based products, and engage the international community to enhance biotechnology R&D cooperation in a way that is consistent with United States principles and values.

The governments penchant for controversial biotechnology long predates the Biden administration. In 2001, a New York Times investigation found that American defense agencies under Presidents George W. Bush and Bill Clinton had continued to experiment with biological weapons, despite a 1972 international treaty prohibiting them. In 2011, The Guardian revealed that the CIA under President Barack Obama organized a fake Hepatitis B vaccine drive in Pakistan that sought to locate family members of Osama bin Laden through nonconsensual DNA collection, leading the agency to eventually promise a cessation of falseimmunization campaigns.

CIA Labs, a 2020 initiative overseen by Donald Trumps CIA director, Gina Haspel infamous for running a torture laboratory in Thailand follows a model similar to In-Q-Tels. The program created a research network to incubate top talent and technology for use across U.S. defense agencies, while simultaneously allowing participating CIA officers to personally profit off their research and patents.

In-Q-Tel board members are allowed to sit on the boards of companies in which the firm invests, raising ethics concerns over howthe non-profit selects companies to back with government dollars. A 2016 Wall Street Journal investigation found that almost half of In-Q-Tel board members were connected to the companies where it had invested.

The size of In-Q-Tels stake in Colossal wont be known until the nonprofit releases its financial statements next year, but the investment may provide a boon on reputation alone: In-Q-Tel has claimed that every dollar it invests in a business attracts 15 more from other investors.

Colossals co-founders, Lamm and Church, represent the ventures business and science minds, respectively. Lamm, a self-proclaimed serial technology entrepreneur, founded his first company as a senior in college, then pivoted to mobile apps and artificial intelligence before helping to start Colossal.

Church a Harvard geneticist, genome-based dating app visionary, and former Jeffrey Epstein funding recipient has proposed the revival of extinct species before. Speaking to Der Spiegel in 2013, Church suggested the resurrection of the Neanderthal an idea met with controversy because it would require technology capable of human cloning.

We can clone all kinds of mammals, so its very likely that we could clone a human, Church said. Why shouldnt we be able to do so? When the interviewer reminded him of a ban on human cloning, Church said, And laws can change, by the way.

Even when the methods used for de-extinction are legal, many scientists are skeptical of its promise. In a 2017 paper for Nature Ecology & Evolution, a group of biologists from Canada, Australia, and New Zealand found that [s]pending limited resources on de-extinction could lead to net biodiversity loss.

De-extinction is a fairytale science, Jeremy Austin, a University of Adelaide professor and director of the Australian Center for Ancient DNA,toldthe Sydney Morning Herald over the summer, when Colossal pledged to sink $10 million into the University of Melbourne for its Tasmanian tiger project. Its pretty clear to people like me that thylacine or mammoth de-extinction is more about media attention for the scientists and less about doing serious science.

Critics who say de-extinction of genes to create proxy species is impossible are critics who are simply not fully informed and do not know the science. We have been clear from day one that on the path to de-extinction we will be developing technologies which we hope to be beneficial to both human healthcare as well as conservation, Lamm wrote to The Intercept. We will conitnue [sic] to share these technologies we develop with the world.

It remains to be seen if Colossal, with In-Q-Tels backing, can make good on its promises. And its unclear what, exactly, the intelligence world might gain from the use of CRISPR. But perhaps the CIA shares the companys altruistic, if vague, motives: To advance the economies of biology and healing through genetics. To make humanity more human. And to reawaken the lost wilds of Earth. So we, and our planet, can breathe easier.

Update: September 28, 2022, 1:00 p.m. ETThis story has been updated with a statement from Colossal co-founder Ben Lamm.

Genetics

Invitae Appointed to National Quality Forum Committee on Quality Standards for Healthcare – PR Newswire

October 3, 2022 medical

First genetics testing company to sit on Forum

Genetics perspective on committee will accelerate healthcare quality standards aligning with medical and technological advancements

SAN FRANCISCO, Sept. 27, 2022 /PRNewswire/ -- Invitae (NYSE: NVTA), a leading medical genetics company, today announced the company has received a three-year appointment to a National Quality Forum (NQF) committee that provides input on recommendations for quality standards that impact how healthcare is delivered. Invitae is the first genetics testing company to join the Measure Applications Partnership (MAP) Clinician workgroup committee, representing a critical step in making genetics the standard of care in mainstream medicine and potentially improving healthcare for billions.

The MAP Clinician workgroup is a multi-stakeholder partnership with organizations such as health plans and provider organizations tasked with providing recommendations to the U.S. Department of Health and Human Services on the selection and removal of performance measures for federal public reporting, performance-based payment and other health programs.

"The selection of Invitae to the MAP Clinician workgroup indicates the National Quality Forum is prioritizing genomics for their work in setting standards for quality healthcare. I am glad to see NQF playing an active role to help incentivize this progress of medicine and applaud their choice of Invitae. I look forward to Invitae's contributions in this partnership," said Christine Cassel, MD, former NQF president and CEO and former planning dean for Kaiser Permanente's School of Medicine.

The MAP Clinician workgroup plays an important role for NQF's evaluation and endorsement process for implementation of standardized healthcare performance measures. Both public and private payers use measures for a variety of accountability purposes, including public reporting and performance-based payment programs. Measures are an essential part of making the quality and cost of healthcare more transparent to all, which is important for those who receive care or make care decisions for loved ones. Use of standardized healthcare performance measures allows for comparison across clinicians, hospitals, health plans and other providers.

"We believe healthcare quality, equity and patient safety cannot be addressed without the recognition that genetics plays a critical role. With this consideration, quality standards can help providers and health plans keep up with the evidence, clinical guidelines and advancement of medicine," said Chantelle Schenning, PhD, MHA, head of healthcare transformation at Invitae. "NQF's decision to invite our voice to represent the genetics perspective and expertise creates a more balanced, diverse stakeholder group that better aligns with advancements in clinical care seen in the outpatient setting today."

Each year, millions of people are screened for or diagnosed with diseases for which their genetic information can be clinically actionable for them and their families. As genetic information becomes increasingly important in driving healthcare decision-making and outcomes, quality standards should reflect and encourage the relevant use of genetics in clinical practice to help treat and prevent disease. If incorporated appropriately, the inclusion of genetics in quality measures could reduce (rather than widen) existing disparities in patient outcomes in cancer, cardiovascular disease, pediatrics and many others.

About the National Quality ForumThe National Quality Forum (NQF) works with members of the healthcare community to drive measurable health improvements together. NQF is a not-for-profit, membership-based organization that gives all healthcare stakeholders a voice in advancing quality measures and improvement strategies that lead to better outcomes and greater value. Learn more at http://www.qualityforum.org.

About InvitaeInvitae Corporation (NYSE: NVTA) is a leading medical genetics company, whose mission is to bring comprehensive genetic information into mainstream medicine to improve healthcare for billions of people. Invitae's goal is to aggregate the world's genetic tests into a single service with higher quality, faster turnaround time and lower prices. For more information, visit the company's website at invitae.com.

Safe Harbor StatementThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements relating to the company's beliefs regarding its appointment to the NQF committee, including that it will accelerate healthcare quality standards aligning with medical and technological advancements and that it represents a critical step in making genetics the standard of care in mainstream medicine and potentially improving healthcare for billions; and the company's belief that the inclusion of genetics in quality measures could reduce existing disparities in patient outcomes in many diseases. Forward-looking statements are subject to risks and uncertainties that could cause actual results to differ materially, and reported results should not be considered as an indication of future performance. These risks and uncertainties include, but are not limited to: the company's history of losses; the company's ability to compete; the company's failure to manage growth effectively; the company's need to scale its infrastructure in advance of demand for its tests and to increase demand for its tests; the company's ability to use rapidly changing genetic data to interpret test results accurately and consistently; security breaches, loss of data and other disruptions; laws and regulations applicable to the company's business; and the other risks set forth in the company's filings with the Securities and Exchange Commission, including the risks set forth in the company's Quarterly Report on Form 10-Q for the quarter ended June 30, 2022. These forward-looking statements speak only as of the date hereof, and Invitae Corporation disclaims any obligation to update these forward-looking statements.

Contact:Renee Kelley[emailprotected](628) 213-3283

SOURCE Invitae Corporation

Genetics

It was a perfect storm: How 13 rabbits caused the largest biological invasion in history – EL PAS USA

October 3, 2022 medical

On Christmas Eve, 1859, 24 rabbits arrived at Thomas Austins hunting estate near Sydney in eastern Australia. Just two months earlier, his brother William Austin had sent him 13 rabbits from southern England. Three years later, the local press reported that there were already thousands of European leporids in the country. Thomas himself acknowledged that he had slaughtered 20,000 of the animals on his property. By 1906, the rabbits had reached Australias west coast, 4,000 kilometers (about 2,485 miles) away from Thomas Austins property. Now, a genetic study confirms that the Austin brothers rabbits started the largest biological invasion ever recorded.

The contemporary press and history books note the Austins culpability in the disaster. Even Williams granddaughter, Joan Palmer, tells her version of the story in her memoirs. But many scientists and historians acknowledge that its more complicated than that: the English settled in Australia in 1788, when the ships of the First Fleet arrived on a mission for the British crown to turn the huge island into a penal colony. Five rabbits were aboard one of the ships that made the voyage. Records show that there were another 90 shipments of rabbits over the next 70 years. Some of the animals escaped or were released deliberately, but none of them caused a biological invasion. The proliferation of wild rabbits has damaged Australian ecosystems and cornered marsupials; rabbits are the continents main agricultural pests. For over a century and a half, Australians have tried everything to stop the invasion, from rifles and fences, to ferrets and phosphorus poisons, to viruses and bacteria. So, what happened on Christmas Eve in 1859?

A group of British, Portuguese and Australian researchers have used genetics to confirm the Austin brothers responsibility for the disaster. The scientists analyzed the genes of almost 200 rabbits from Spain (the common rabbits place of origin), France (where the animals were domesticated during the Middle Ages), England, Australia and two other countries that also suffered the scourge: neighboring New Zealand and Tasmania. Several specimens come from a few years after the invasion began. This data allowed the scientists to create a genetic tree to study how the rabbits proliferation occurred. The researchers published their findings in the scientific journal PNAS (Proceedings of the National Academy of Sciences of the United States of America).

Their wild ancestry probably gave these rabbits an advantage, as they were better adapted to the harsh Australian landscape

Joel Alves, a researcher at the University of Oxford and the Research Center for Biodiversity and Genetic Resources in Portugal, and the studys lead author, explains what they hoped to find by recreating the rabbit gene tree: We looked for a combination of different genetic markers that we expect when populations expand. Importantly, they saw that almost all Australian rabbits are closely related, despite being separated by thousands of kilometers. Something like that would not have been possible if there had been other successful introductions, notes Alves. He adds that the further away the rabbit populations are from Victoria [the state where the invasion originated], the less genetic diversity they have. This is to be expected from a large significant expansion from a single place, because genetic diversity erodes as individuals expand rapidly. Biologists call this the founder effect.

Analysis of mitochondrial DNA, which is inherited exclusively through the maternal line, has allowed the researchers to estimate the number of females behind the proliferation of hundreds of millions of Australian rabbits: William sent only five females to Thomas. Genetics has also helped the scientists confirm the rabbits geographical origin. On the European branches of the genetic tree, the Australian rabbits are closest to the ones connected to the United Kingdoms southwest, where William Austins land was located. But what was so special about the Austin rabbits as compared to the ones that arrived in Australia earlier?

We have historical and genetic evidence that most of the previous introductions were domestic rabbits. Austins are the only ones explicitly described as wild and captured in a natural environment, which we have confirmed genetically, says Alves. One piece of historical proof is the memoir of Joan Palmer, William Austins granddaughter. She recalls that Thomas asked William to send him a dozen wild rabbits to release on his hunting grounds. The emigrant belonged to one of the acclimatization societies that sprang up in the 19th century. These associations imported species from their homelands to introduce them into the colonies, out of both longing and economic interests. But that had dire consequences in the many ecosystems exposed simultaneously to the actions of white settlers and invasive species. In the Austins case, William captured only six wild rabbits and bought another seven from neighbors who had trapped the animals as young and then domesticated them. The rabbits had to interbreed during the journey to match the 24 animals that appear in the historical records.

Alves explains their wild ancestry probably gave these rabbits an advantage, because they were better adapted to the harsh Australian landscape. In addition to their gray to brownish coloration, which is ideal for camouflage in the dry, semi-arid terrain, the wild rabbits retained their flight response to danger. Domestic rabbits are an easier target for predators because they have lost that reaction and are more docile and more strikingly colored.

In Australia rabbits have evolved with changes in body shape to help regulate their temperature

Francis Jiggins, a professor of genetics at the University of Cambridge and a senior author of the study, notes that there are numerous traits that could make domestic rabbits of wild origin poorly adapted for survival in the wild, but it is possible that they lacked the genetic variation needed to adapt to Australias arid and semi-arid climate. He concludes that to cope with this [environment], Thomas Austins wild rabbits and their offspring had a genetic advantage in adapting to these conditions.

Martn Nuez, a researcher at the University of Houston and an expert in invasion ecology, says that the investigations results are compelling, although they are at odds with previous research that finds rabbits spread throughout Australia from different places at different times. [Determining] why some species invade and others dont is invasion biologys holy grail. Weve been trying to find that out for decades. This study didnt find the holy grail, but it provides information about the processes through which it can happen, he explains. Nuez notes that the research shows that its not so much about the species, but about a population of potentially pre-adapted individuals. This work also demonstrates that the view of rabbits as a highly invasive species, at least outside of Europe, is wrong, since here it is very clear that a given population at a specific time was responsible [for the biological invasion], while other populations had much more limited success.

Alves acknowledges that genetics are not the only explanation for the invasion: It is likely that changes in the environment also played a role when the Austin rabbits arrived. Australia in 1788 was very different from Australia in 1859; by the mid-19th century, the country had extensive grazing land that could feed rabbits, and herders killed fewer predators. So, it was the perfect storm; the right rabbits were in the right place at the right time.

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It was a perfect storm: How 13 rabbits caused the largest biological invasion in history - EL PAS USA

Neuroscience

NYU Neuro Grad Program – Home

October 3, 2022 medical

Understanding the brain is one of the great scientific challenges. How does the nervous system allow us to sense, move, learn, decide, remember, and think? How are the underlying neural circuits built by genetic and molecular programs? How do neurons communicate via synapses to transmit and store information? What goes wrong in neurodevelopmental disorders like autism and schizophrenia, and in neurodegenerative diseases like Alzheimers and Parkinsons disease? And how can we model neurons, circuits and systems to better understand the brain?Graduate students in our PhD program in neuroscience are addressing these questions at labs located across NYU, using cutting-edge tools drawn from genetics, molecular biology, biochemistry, electrophysiology, microscopy, computer science, data science, and mathematics.This website is designed for you to learn about graduate training in neuroscience at NYU.Our program arises from two cooperative centers located just a few city blocks apart: the Center for Neural Science (CNS) and the Neuroscience Institute (NI). CNS, located at NYUs Washington Square campus, is home to core neuroscience labs, has affiliate labs in biology, psychology, physics and data science, and is NYUs portal for undergraduate neuroscience education. The NI is located at NYUs school of medicine and houses additional core neuroscience labs, as well as affiliates from clinical departments and the Nathan Kline Institute. Together, CNS and NI serve as the joint pillars of graduate training in neuroscience at NYU, with research spanning genetic, molecular, cellular, developmental, systems, behavioral, and computational levels. Prospective graduate students apply through a single online portal and applications are jointly reviewed by a single admissions committee that spans CNS and NI.

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NYU Neuro Grad Program - Home

Neuroscience

Neuroscience | OhioHealth

October 3, 2022 medical

At OhioHealth, we provide the most comprehensive neuroscience care to diagnose, treat and heal patients with conditions like ALS, multiple sclerosis, Parkinsons disease, epilepsy, spine pain, stroke and more. We involve the highest-skilled specialists, the latest medical advancements, clinical trials and exclusive wellness programs to develop individualized treatment plans.

Providing new pathways for neuroscience research and education – MIT News

October 3, 2022 medical

Payton Dupuiss interest in biology research began where it does for many future scientists witnessing a relative struggling with an incurable medical condition. For Dupuis, that family member was her uncle, who suffered from complications from diabetes. Dupuis, a senior at Montana State University, says that diabetes is prominent on the Flathead Reservation in Montana, where she grew up, and witnessing the impacts of the disease inspired her to pursue a career in scientific research. Since then, that passion has taken Dupuis around the country to participate in various summer research programs in the biomedical sciences.

Most recently, she was a participant in the Bernard S. and Sophie G. Gould MIT Summer Research Program in Biology (BSG-MSRP-Bio). The program, offered by the departments of Biology and Brain and Cognitive Sciences, is designed to encourage students from underrepresented groups to attend graduate school and pursue careers in science research. More than 85 percent of participants have subsequently enrolled in highly ranked graduate programs, many of them returning to MIT, just as Dupuis is considering.

Her journey from witnessing the impacts of her uncles diabetes to considering graduate school at MIT was made possible only by Dupuiss love of science and her ability to find a positive, as she says, in every experience.

As a high-schooler, Dupuis made her first trip to the Northeast, participating in the Summer Academy of Math and Sciences at Carnegie Mellon University. For Dupuis, who hadnt even taken calculus yet, the experience was a welcome challenge. That definitely made me work hard, she laughs, comparing herself to other program participants. But I proved to myself, not for anyone else, that I belonged in that program.

In addition to being a confidence booster, the Carnegie Mellon program also gave Dupuis her first taste of scientific research working in a biomedical lab on tissue regeneration. She was excited about the possibilities of growing new organs such as the insulin-producing pancreas that could help regulate her uncles diabetes outside of the body. Dupuis was officially hooked on biology.

Her experience that summer encouraged Dupuis to major in chemical engineering, seeing it as a good pipeline into biomedical research. Unfortunately, the chemical engineering curriculum at Montana State wasnt what she expected, focusing less on the human body and more on the oil industry. In that context, her ability to see a silver lining served Dupuis well.

That wasnt really what I wanted, but it was still interesting because there were ways that I could apply it to the body, she explains. Like fluid mechanics instead of water flowing through a pipe, I was thinking about blood flowing through veins.

Dupuis adds that the chemical engineering program also gave her problem-solving skills that have been valuable as shes undertaken biology-focused summer programs to help refine her interests. One summer, she worked in the chemistry department at Montana State, getting hands-on experience in a wet lab. I didnt really know any of the chemistry behind what I was doing, she admits, but I fell in love with it. Another summer, she participated in the Tufts Building Diversity in Biomedical Sciences program, exploring the genetic side of research through a project on bone development in mice.

In 2020, a mentor at the local tribal college connected Dupuis with Keith Henry, an associate professor of biomedical sciences at the University of North Dakota. With Henry, Dupuis looked for new binding sites for the neurotransmitter serotonin that could help minimize the side effects that come with long-term use of selective serotonin reuptake inhibitors (SSRIs), the most common class of antidepressants. That summer was Dupuiss first exposure to brain research, and her first experience modeling biological processes with computers. She loved it. In fact, as soon as she returned to Montana State, Dupuis enrolled as a computer science minor.

Because of the minor, Dupuis needs an extra year to graduate, which left her one more summer for a research program. Her older sister had previously participated in the general MSRP program at MIT, so it was a no-brainer for Dupuis to apply for the biology-specific program.

This summer, Dupuis was placed in the lab of Troy Littleton, the Menicon Professor in Neuroscience at The Picower Institute for Learning and Memory. I definitely fell in love with the lab, she says. With Littleton, Dupuis completed a project looking at complexin, a protein that can both inhibit and facilitate the release of neurotransmitters like serotonin. Its also essential for the fusion of synaptic vesicles, the parts of neurons that store and release neurotransmitters.

A number of human neurological diseases have been linked to a deficiency in complexin, although Dupuis says that scientists are still figuring out what the protein does and how it works.

To that end, Dupuis focused this summer on fruit flies, which have two different types of complexin humans, in comparison, have four. Using gene editing, she designed an experiment comparing fruit flies possessing various amounts of different subtypes of the protein. There was the positive control group, which was untouched; the negative control group that had no complexin; and two experimental groups, each with one of the subtypes removed. Using fluorescent staining, Dupuis compared how neurons lit up in each group of flies, illuminating how altering the amount of complexin changed how the flies released neurotransmitters and formed new synaptic connections.

After touching on so many different areas of biological research through summer programs, Dupuis says that researching neuronal activity in fruit flies this summer was the perfect fit intellectually, and a formative experience as a researcher.

Ive definitely learned how to take an experiment and make it my own and figure out what works best for me, but still produces the results we need, she says.

As for whats next, Dupuis says her experience at MIT has sold her on pursuing graduate work in brain sciences. Boston is really where I want to be and eventually work, with all the biotech and biopharma companies around, she says. One of the perks of the MSRP-Bio program is professional development opportunities. Though Dupuis had always been interested in industry, she says she appreciated attending career panels this summer that demystified what that career path really looks like and what it takes to get there.

Perhaps the most important aspect of the program for Dupuis, though, was the confidence it provided as she continues to navigate the world of biomedical research. She intends to take that back with her to Montana State to encourage classmates to seek out similar summer opportunities.

Theres so many people that I know would be a great researcher and love science, but they just dont either know about it or think they can get it, she says. All Id say is, you just got to apply. You just have to put yourself out there.

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Providing new pathways for neuroscience research and education - MIT News

Neuroscience

Study Reveals Main Target of COVID-19 in Brain and Describes Effects of Virus on Nervous System – Neuroscience News

October 3, 2022 medical

Summary: SARS_CoV_2, the virus responsible for COVID-19 infects and replicates in astrocytes, reducing neural viability.

Source: FAPESP

A Brazilian study published in the journalPNASdescribes some of the effects infection by SARS-CoV-2 can have on the central nervous system.

A preliminary version (not yet peer-reviewed) posted in 2020 was one of the first to show that the virus that causes COVID-19 can infect brain cells, especially astrocytes. It also broke new ground by describing alterations in the structure of the cortex, the most neuron-rich brain region, even in cases of mild COVID-19.

The cerebral cortex is the outer layer of gray matter over the hemispheres. It is the largest site of neural integration in thecentral nervous systemand plays a key role in complex functions such as memory, attention, consciousness, and language.

The investigation was conducted by several groups at the State University of Campinas (UNICAMP) and the University of So Paulo (USP). Researchers at the Brazilian Biosciences National Laboratory (LNBio), DOr Institute (IDOR) and the Federal University of Rio de Janeiro (UFRJ) also contributed to the study.

Two previous studies detected the presence of the novel coronavirus in the brain, but no one knew for sure if it was in the bloodstream,endothelial cells[lining the blood vessels] or nerve cells. We showed for the first time that it does indeed infect and replicate in astrocytes, and that this can reduce neuron viability, Daniel Martins-de-Souza, one of the leaders of the study, told Agncia FAPESP. Martins-de-Souza is a professor at UNICAMPs Biology Institute and a researcher affiliated with IDOR.

Astrocytes are the most abundant central nervous system cells. Their functions include providing biochemical support and nutrients for neurons; regulating levels of neurotransmitters and other substances that may interfere with neuronal functioning, such as potassium; maintaining the blood-brain barrier that protects the brain from pathogens and toxins; and helping to maintain brain homeostasis.

Infection of astrocytes was confirmed by experiments using brain tissue from 26 patients who died of COVID-19. The tissue samples were collected during autopsies conducted using minimally invasive procedures by Alexandre Fabro, a pathologist and professor at the University of So Paulos Ribeiro Preto Medical School (FMRP-USP). The analysis was coordinated by Thiago Cunha, also a professor in FMRP-USP and a member of the Center for Research on Inflammatory Diseases (CRID).

The researchers used a technique known as immunohistochemistry, a staining process in which antibodies act as markers of viral antigens or other components of the tissue analyzed.

For example, we can insert one antibody into the sample to turn the astrocytes red on binding to them, another to mark the SARS-CoV-2 spike protein by making it green, and a third to highlight the viruss double-stranded RNA, which only appears during replication, by turning it magenta, Martins-de-Souza explained.

When the images produced during the experiment were overlaid, all three colors appeared simultaneously only in astrocytes.

According to Cunha, the presence of the virus was confirmed in five of the 26 samples analyzed. Alterations suggesting possible damage to the central nervous system were also found in these five samples.

We observed signs of necrosis and inflammation, such as edema [swelling caused by a buildup of fluid], neuronal lesions and inflammatory cell infiltrates, he said.

The capacity of SARS-CoV-2 to infect brain tissue and its preference for astrocytes were confirmed by Adriano Sebolella and his group at FMRP-USP using the method of brain-derived slice cultures, an experimental model in which human brain tissue obtained during surgery to treat neurological diseases such as drug-refractory epilepsy, for example, is cultured in vitro and infected with the virus.

Persistent symptoms

In another part of the research, conducted in UNICAMPs School of Medical Sciences (FCM), 81 volunteers who had recovered from mild COVID-19 were submitted to magnetic resonance imaging (MRI) scans of their brains.

These scans were performed 60 days after diagnostic testing on average. A third of the participants still had neurological or neuropsychiatric symptoms at the time. They complained mostly of headache (40%), fatigue (40%), memory alterations (30%), anxiety (28%), loss of smell (28%), depression (20%), daytime drowsiness (25%), loss of taste (16%) and low libido (14%).

We posted a link for people interested in participating in the trial to register, and were surprised to get more than 200 volunteers in only a few days. Many were polysymptomatic, with widely varying complaints. In addition to the neuroimaging exam, theyre being evaluated neurologically and taking standardized tests to measure performance in cognitive functions such as memory, attention and mental flexibility. In the article we present the initial results, said Clarissa Yasuda, a professor and member of the Brazilian Research Institute for Neuroscience and Neurotechnology (BRAINN).

Only volunteers diagnosed with COVID-19 by RT-PCR and not hospitalized were included in the study. The assessments were carried out after the end of the acute phase, and the results were compared with data for 145 healthy uninfected subjects.

The MRI scans showed that some volunteers had decreased cortical thickness in some brain regions compared with the average for controls.

We observed atrophy in areas associated, for example with anxiety, one of the most frequent symptoms in the study group, Yasuda said. Considering that the prevalence of anxiety disorders in the Brazilian population is 9%, the 28% we found is an alarmingly high number. We didnt expect these results in patients who had had the mild form of the disease.

In neuropsychological tests designed to evaluate cognitive functioning, the volunteers also underperformed in some tasks compared with the national average. The results were adjusted for age, sex and educational attainment, as well as the degree of fatigue reported by each participant.

The question were left with is this: Are these symptoms temporary or permanent? So far, weve found that some subjects improve, but unfortunately many continue to experience alterations, Yasuda said.

Whats surprising is that many people have been reinfected by novel variants, and some report worse symptoms than they had since the first infection. In view of the novel virus, we see longitudinal follow-up as crucial to understand the evolution of the neuropsychiatric alterations over time and for this understanding to serve as a basis for the development of targeted therapies.

Energy metabolism affected

In IB-UNICAMPs Neuroproteomics Laboratory, which is headed by Martins-de-Souza, experiments were performed on brain tissue cells from people who died of COVID-19 and astrocytes cultured in vitro to find out how infection by SARS-CoV-2 affects nervous system cells from the biochemical standpoint.

The autopsy samples were obtained via collaboration with the group led by Paulo Saldiva, a professor at the University of So Paulos Medical School (FM-USP). The proteome (all proteins present in the tissue) was mapped using mass spectrometry, a technique employed to identify different substances in biological samples according to their molecular mass.

When the results were compared with those of uninfected subjects, several proteins with altered expression were found to be abundant in astrocytes, which validated the findings obtained by immunohistochemistry, Martins-de-Souza said.

We observed alterations in various biochemical pathways in the astrocytes, especially pathways associated withenergy metabolism.

The next step was to repeat theproteomic analysisin cultured astrocytes infected in the laboratory. The astrocytes were obtained from induced pluripotent stem cells (iPSCs). The method consists of reprogramming adult cells (derived from skin or other easily accessible tissues) to assume a stage of pluripotency similar to that of embryo stem cells.

This first part was conducted in the IDOR laboratory of Stevens Rehen, a professor at UFRJ. Martins-de-Souzas team then used chemical stimuli to make the iPSCs differentiate into neural stem cells and eventually into astrocytes.

The results were similar to those of the analysis of tissue samples obtained by autopsy in that they showed energy metabolism dysfunction, Martins-de-Souza said.

We then performed a metabolomic analysis [focusing on the metabolites produced by the cultured astrocytes], which evidenced glucose metabolism alterations. For some reason, infected astrocytes consume more glucose than usual, and yet cellular levels of pyruvate and lactate, the main energy substrates, decreased significantly.

Lactate is one of the products of glucose metabolism, and astrocytes export this metabolite to neurons, which use it as an energy source. The researchers in vitro analysis showed that lactate levels in the cell culture medium were normal but decreased inside the cells. Astrocytes appear to strive to maintain the energy supply to neurons even if this effort weakens their own functioning, Martins-de-Souza said.

As an outcome of this process, the functioning of the astrocytes mitochondria (energy-producing organelles) was indeed altered, potentially influencing cerebral levels of such neurotransmitters as glutamate, which excites neurons and is associated with memory and learning, or gamma-aminobutyric acid (GABA), which inhibits excessive firing of neurons and can promote feelings of calm and relaxation.

In another experiment, we attempted to culture neurons in the medium where the infected astrocytes had grown previously and measured a higher-than-expected cell death rate. In other words, this culture medium conditioned by infected astrocytes weakened neuron viability, Martins-de-Souza said.

The findings described in the article confirm those of several previously published studies pointing to possible neurological and neuropsychiatric manifestations of COVID-19.

Results of experiments on hamsters conducted at the Institute of Biosciences (IB-USP), for example, reinforce the hypothesis that infection by SARS-CoV-2 accelerates astrocyte metabolism and increases the consumption of molecules used to generate energy, such as glucose and the amino acid glutamine.

The results obtained by the group led by Jean Pierre Peron indicate that this metabolic alteration impairs the synthesis of a neurotransmitter that plays a key role in communication among neurons.

Unanswered questions

According to Martins-de-Souza, there is no consensus in the scientific literature on how SARS-CoV-2 reaches the brain.

Some animal experiments suggest the virus can cross the blood-brain barrier. Theres also a suspicion that it infects the olfactory nerve and from there invades the central nervous system. But these are hypotheses for now, he said.

One of the discoveries revealed by thePNASarticle is that the virus does not use the protein ACE-2 to invade central nervous system cells, as it does in the lungs.

Astrocytes dont have the protein in their membranes. Research by Flvio Veras [FMRP-USP] and his group shows that SARS-CoV-2 binds to the protein neuropilin in this case, illustrating its versatility in infecting different tissues, Martins-de-Souza said.

At UNICAMPs Neuroproteomics Laboratory, Martins-de-Souza analyzed nerve cells and others affected by COVID-19, such as adipocytes, immune system cells and gastrointestinal cells, to see how the infection altered the proteome.

Were now compiling the data to look for peculiarities and differences in the alterations caused by the virus in these different tissues. Thousands of proteins and hundreds of biochemical pathways can be altered, with variations in each case. This knowledge will help guide the search for specific therapies for each system impaired by COVID-19, he said.

Were also comparing the proteomic differences observed inbrain tissuefrom patients who died of COVID-19 with proteomic differences weve found over the years in patients with schizophrenia. The symptoms of both conditions are quite similar. Psychosis, the most classic sign of schizophrenia, also occurs in people with COVID-19.

The aim of the study is to find out whether infection by SARS-CoV-2 can lead to degeneration of the white matter in the brain, made up mainly of glial cells (astrocytesand microglia) and axons (extensions of neurons).

Weve observed a significant correspondence [in the pattern of proteomic alterations] associated with the energy metabolism and glial proteins that appear important in both COVID-19 and schizophrenia. These findings may perhaps provide a shortcut to treatments for the psychiatric symptoms of COVID-19, Martins-de-Souza pondered.

Marcelo Mori, a professor at IB-UNICAMP and a member of the Obesity and Comorbidities Research Center (OCRC), the study was only possible thanks to the collaboration of researchers with varied and complementary backgrounds and expertise.

It demonstrates that first-class competitive science is always interdisciplinary, he said. Its hard to compete internationally if you stay inside your own lab, confining yourself to the techniques with which youre familiar and the equipment to which you have access.

Author: Press OfficeSource: FAPESPContact: Press Office FAPESPImage: The image is in the public domain

Original Research: Open access.Morphological, cellular, and molecular basis of brain infection in COVID-19 patients by Fernanda Crunfli et al. PNAS

Abstract

Morphological, cellular, and molecular basis of brain infection in COVID-19 patients

Although increasing evidence confirms neuropsychiatric manifestations associated mainly with severe COVID-19 infection, long-term neuropsychiatric dysfunction (recently characterized as part of long COVID-19 syndrome) has been frequently observed after mild infection.

We show the spectrum of cerebral impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, ranging from long-term alterations in mildly infected individuals (orbitofrontal cortical atrophy, neurocognitive impairment, excessive fatigue and anxiety symptoms) to severe acute damage confirmed in brain tissue samples extracted from the orbitofrontal region (via endonasal transethmoidal access) from individuals who died of COVID-19. In an independent cohort of 26 individuals who died of COVID-19, we used histopathological signs of brain damage as a guide for possible SARS-CoV-2 brain infection and found that among the 5 individuals who exhibited those signs, all of them had genetic material of the virus in the brain.

Brain tissue samples from these five patients also exhibited foci of SARS-CoV-2 infection and replication, particularly in astrocytes.

Supporting the hypothesis of astrocyte infection, neural stem cellderived human astrocytes invitro are susceptible to SARS-CoV-2 infection through a noncanonical mechanism that involves spikeNRP1 interaction. SARS-CoV-2infected astrocytes manifested changes in energy metabolism and in key proteins and metabolites used to fuel neurons, as well as in the biogenesis of neurotransmitters. Moreover, human astrocyte infection elicits a secretory phenotype that reduces neuronal viability.

Our data support the model in which SARS-CoV-2 reaches the brain, infects astrocytes, and consequently, leads to neuronal death or dysfunction. These deregulated processes could contribute to the structural and functional alterations seen in the brains of COVID-19 patients.

Originally posted here:
Study Reveals Main Target of COVID-19 in Brain and Describes Effects of Virus on Nervous System - Neuroscience News

Neuroscience

Love Hormone Oxytocin Could Mend a Broken Heart – Neuroscience News

October 3, 2022 medical

Summary: Oxytocin, a hormone connected with bonding and love, could help to heal damage following a heart attack. Researchers found oxytocin stimulates stem cells from the hearts outer layer and migrates into the middle layer where it develops into muscle cells that generate heart contractions. This could be used to promote the regeneration of heart cells following a heart attack.

Source: Frontiers

The neurohormone oxytocin is well-known for promoting social bonds and generating pleasurable feelings, for example from art, exercise, or sex. But the hormone has many other functions, such as the regulation of lactation and uterine contractions in females, and the regulation of ejaculation, sperm transport, and testosterone production in males.

Now, researchers from Michigan State University show that in zebrafish and human cell cultures, oxytocin has yet another, unsuspected, function: it stimulates stem cells derived from the hearts outer layer (epicardium) to migrate into its middle layer (myocardium) and there develop into cardiomyocytes, muscle cells that generate heart contractions. This discovery could one day be used to promote the regeneration of the human heart after a heart attack.

The results are published inFrontiers in Cell and Developmental Biology.

Here we show that oxytocin, a neuropeptide also known as the love hormone, is capable of activating heart repair mechanisms in injured hearts in zebrafish and human cell cultures, opening the door to potential new therapies for heart regeneration in humans, said Dr Aitor Aguirre, an assistant professor at the Department of Biomedical Engineering of Michigan State University, and the studys senior author.

Stem-like cells can replenish cardiomyocytes

Cardiomyocetes typically die off in great numbers after a heart attack. Because they are highly specialized cells, they cant replenish themselves. But previous studies have shown that a subset of cells in the epicardium can undergo reprogramming to become stem-like cells, called Epicardium-derived Progenitor Cells (EpiPCs), which can regenerate not only cardiomyocytes, but also other types of heart cells.

Think of the EpiPCs as the stonemasons that repaired cathedrals in Europe in the Middle Ages, explained Aguirre.

Unfortunately for us, the production of EpiPCs is inefficient for heart regeneration in humans under natural conditions.

Zebrafish could teach us how to regenerate hearts more efficiently

Enter the zebrafish: famous for their extraordinary capacity for regenerating organs, including the brain, retina, internal organs, bone, and skin. They dont suffer heart attacks, but its many predators are happy to take a bite out of any organ, including the heart so zebrafish can regrow their heart when as much as a quarter of it has been lost.

This is done partly by proliferation of cardiomyocytes, but also by EpiPCs. But how do the EpiPCs of zebrafish repair the heart so efficiently? And can we find a magic bullet in zebrafish that could artificially boost the production of EpiPCs in humans?

Yes, and this magic bullet appears to be oxytocin, argue the authors.

To reach this conclusion, the authors found that in zebrafish, within three days after cryoinjury injury due to freezing to the heart, the expression of the messenger RNA for oxytocin increases up to 20-fold in the brain.

They further showed that this oxytocin then travels to the zebrafish epicardium and binds to the oxytocin receptor, triggering a molecular cascade that stimulates local cells to expand and develop into EpiPCs.

These new EpiPCs then migrate to the zebrafish myocardium to develop into cardiomyocytes, blood vessels, and other important heart cells, to replace those which had been lost.

Similar effect on human tissue cultures

Crucially, the authors showed that oxytocin has a similar effect on human tissuein vitro. Oxytocin but none of 14 other neurohormones tested here stimulates cultures of human Induced Pluripotent Stem Cells (hIPSCs) to become EpiPCs, at up to twice the basal rate: a much stronger effect than other molecules previously shown to stimulate EpiPC production in mice.

Conversely, genetic knock-down of the oxytocin receptor prevented the the regenerative activation of human EpiPCs in culture. The authors also showed that the link between oxytocin and the stimulation of EpiPCs is the important TGF- signaling pathway, known to regulate the growth, differentiation, and migration of cells.

Aguirre said: These results show that it is likely that the stimulation by oxytocin of EpiPC production is evolutionary conserved in humans to a significant extent. Oxytocin is widely used in the clinic for other reasons, so repurposing for patients after heart damage is not a long stretch of the imagination. Even if heart regeneration is only partial, the benefits for patients could be enormous.

Aguirre concluded: Next, we need to look at oxytocin in humans after cardiac injury. Oxytocin itself is short-lived in the circulation, so its effects in humans might be hindered by that. Drugs specifically designed with a longer half-life or more potency might be useful in this setting.

Overall, pre-clinical trials in animals and clinical trials in humans are necessary to move forward.

Author: Mischa DijkstraSource: FrontiersContact: Mischa Dijkstra FrontiersImage: The image is in the public domain

Original Research: Open access.Oxytocin promotes epicardial cell activation and heart regeneration after cardiac injury by Aitor Aguirre et al. Frontiers in Cell and Developmental Biology

Abstract

Oxytocin promotes epicardial cell activation and heart regeneration after cardiac injury

Cardiovascular disease (CVD) is one of the leading causes of mortality worldwide, and frequently leads to massive heart injury and the loss of billions of cardiac muscle cells and associated vasculature.

Critical work in the last 2decades demonstrated that these lost cells can be partially regenerated by the epicardium, the outermost mesothelial layer of the heart, in a process that highly recapitulates its role in heart development.

Upon cardiac injury, mature epicardial cells activate and undergo an epithelial-mesenchymal transition (EMT) to form epicardium-derived progenitor cells (EpiPCs), multipotent progenitors that can differentiate into several important cardiac lineages, including cardiomyocytes and vascular cells.

In mammals, this process alone is insufficient for significant regeneration, but it might be possible to prime it by administering specific reprogramming factors, leading to enhanced EpiPC function.

Here, we show that oxytocin (OXT), a hypothalamic neuroendocrine peptide, induces epicardial cell proliferation, EMT, and transcriptional activity in a model of human induced pluripotent stem cell (hiPSC)-derived epicardial cells.

In addition, we demonstrate that OXT is produced after cardiac cryoinjury in zebrafish, and that it elicits significant epicardial activation promoting heart regeneration. Oxytocin signaling is also critical for proper epicardium development in zebrafish embryos.

The above processes are significantly impaired when OXT signaling is inhibited chemically or genetically through RNA interference. RNA sequencing data suggests that the transforming growth factor beta (TGF-) pathway is the primary mediator of OXT-induced epicardial activation.

Our research reveals for the first time an evolutionary conserved brain-controlled mechanism inducing cellular reprogramming and regeneration of the injured mammalian and zebrafish heart, a finding that could contribute to translational advances for the treatment of cardiac injuries.