Category Archives: Neuroscience

Neuroscience

Stem Cells and Silk Make a New Way to Study the Brain – Tufts Now

More than five million Americans, mostly sixty-five or older, suffer from Alzheimers disease (AD), and that number is expected to triple by 2060, as todays twenty-somethings become seniors. No treatments exist for this devastating disease, and its root causes remain as tangled as the curious brain deformities that German physician Alois Alzheimer first described in 1906.

Now a team of Tufts researchers from the School of Medicine and the School of Engineering has received a five-year, $5 million grant from the National Institute on Aging, part of the National Institutes of Health, to study the role of different cell types and mutations in AD. They will use a unique bioengineered mini brain that realistically simulates the human brain environment for years.

The work, which builds on years of collaboration among the researchers, will overcome two traditional stumbling blocks to such studies: the limited relevance of animal models and the inability of cell culture systems to reproduce the physiology of the human brain. While age is the biggest risk factor for AD, genetics also plays a role. Scientists have uncovered twenty gene variants that increase the risk of AD, said Giuseppina Tesco, professor of neuroscience and lead investigator on the research, who has devoted her career to studying the disease.

Recent studies show that most of the genes that carry these variants are expressed in glial cells, particularly astrocytes and microglial cells. Once dismissed as onlookers in the brain, glia are now front and center in Alzheimers research said glia expert Philip Haydon, a principal investigator on the project. Haydon, the Annetta and Gustav Grisard Professor of Neuroscience, likens these cells to the pit crew for the flashy race-car-like neurons, supporting top performance by, for example, preventing buildup of protein plaques.

But unlike neurons, human glial cells behave very differently from those of other mammals. What we can learn from mouse models is very limited. It is very important to study these genes in human cells, said Tesco. And we need to do this over time. It may take months to see the effect of genetic variation.

The Tufts team will use cells derived from patients with AD as well as healthy subjects, drawing on advanced stem cell technology that makes it possible to reverse engineer human primary cells into induced pluripotent stem cells, which can then differentiate into neurons, astrocytes, and microglia.

These glia and other brain cells will grow on a unique three-dimensional doughnut-shaped scaffold made of porous silk and collagenwhat the researchers have dubbed a mini brain. Bioengineer David Kaplan, Stern Family Professor and a principal investigator on the grant, and his team have spent six years perfecting the mini brain for research on AD, traumatic brain injury, and brain cancer.

This model allows us to put cells where we want, determine ratios of different cells to use in the system, and control interactions, so we can study electrophysiology, synaptic activity, and other functions as the tissue ages, said Kaplan. That control over the long term supports exploration of age-related questions about disease progression and contributes to reproducibility, a scientific pillar. Past experiments using these mini brains have mimicked structural and functional features and neural activity for up to two years.

In contrast, a two-dimensional culture systemlike the proverbial petri dishwont replicate the complexities of multiple cell types and physiologies. And organoidssimplified organs in miniature now in vogueare subject to cellular death after a few weeks or months.

To complement the in vitro studies with the scaffolds, scientists in Haydons lab will transplant some of the human cells, both mutated and normal, into mice. As they grow, the human glia cells will replace the mouse cells, giving researchers an opportunity to study human brain function. This is the first step towards translational studies, said Haydon.

The grant complements donations from Tufts alumni, parents, friends, and other private individuals who have experienced the pain of Alzheimers disease in their own lives. Donor dollars really got some of our early, exploratory work up and running, said Haydon. Now we are building on that.

The NIH support is a bright spot at a time when COVID-19 has forced Tufts scientists, like their peers around the world, to halt laboratory research, sometimes losing years of work.

Tesco said that while it is difficult to be away from her lab, safety is more important than anything else. Im from Italy, where we have more than 22,000 deaths, she said. Being healthy and having the possibility to continue to do some work, I feel lucky. Well be in the best position possible when were ready to start because well be able to start something completely new and very exciting.

Kim Thurler can be reached at kimberly.thurler@tufts.edu.

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Stem Cells and Silk Make a New Way to Study the Brain - Tufts Now

Neuroscience

Kirsten Wade: Wading into the unknown – University of Pittsburgh The Pitt News

Kirsten Wade has a curious case of wanderlust.

Its a habit, the Pitt senior said. I like to go places I dont know, look around and see what I can learn, see if there are new people I can meet.

Thats true in a literal sense. Shes studied abroad four times in Italy, Spain, Switzerland, Germany and Colombia.

But wanderlust sums up Wades life when shes not studying abroad, too. It serves as a metaphor for her meandering interests her passion for art, science, social work and volunteering. In her four years as a Pitt student, Wade has assembled an exhaustive resume encompassing research, mentorship and a whole host of interdisciplinary projects more seamlessly than most people write a grocery list. Shes an urban studies and neuroscience double major with minors in Spanish and chemistry and a concentration in Latin American studies. Thats all landed her a finalist spot for the Rhodes Scholarship, too.

Lets see, Ive done labs for neuro. Ive mentored inner city kids. Ive done internships with urban planning Oh god, what else is on here? she said, grabbing her resume.

A lot, it turns out. Last summer, Wade went to Manizales, Colombia, on a research mission with Pitts Latin American Studies department. One of her favorite memories of the time is taking a spur-of-the moment trip into the idyllic Andes mountains.

But theres a catch.

[Manizales has] a very high risk of a wide variety of natural disasters, Wade said, nonchalantly. Theres an active volcano anything built on the slopes has a risk of landslides.

Wade promises she doesnt have a thirst for danger, just a longing for adventure. But that high risk of landslides and volcanic eruptions brought Wade to Manizales in the first place for research purposes, of course. Her project asked the question: how do people function in their daily lives, knowing that it could be upended by disaster at any time? To find an answer, she surveyed and interviewed people of all different backgrounds in Manizales politicians, Red Cross officials, ordinary citizens and those who had been directly displaced by disasters.

Theres definitely a very present awareness of disasters, Wade said. But most people, for varying reasons, insist it wont affect them.

Since returning from Manizales, Wade has frequented neuroscience labs, done social work at the Birmingham free clinic and taught classes on international urbanism.

Michelle Wade chalks up her little sisters versatility to her insatiable curiosity.

She would have five majors if she could, Michelle told me. Shes always on the hunt for new experiences and opportunities.

I interviewed Kirsten Wade for the first time last spring, when her myriad of interests left her feeling as lost as a wayward traveler are my interests too broad? I hope not, she said, anxiously. This past February, I interviewed her again, and it was like talking to a different person.

Previously, I think I viewed my own curiosity as something I needed to have an answer to all the time. I had curiosities, but I felt too mentally frozen to explore them, Wade said. Now, I realize that not having that answer is the whole point and my curiosity feels so much more real, livable, captivating and insatiable.

For the most part, Wades curiosity has shaped her into a creature of passion someone who wants to help the people she meets and learn everything she possibly can about the human condition. Thats partly how she cultivated an interest in neuroscience.

I remember jokingly telling people [in high school] that I wanted to study brains because of how weird they are, and four to five years later that still somewhat holds true, Wade said.

Wades always been fascinated by how humans come to understand themselves through interacting with the world, she says, and all of that understanding occurs through processes in the brain. But despite the understanding that can arise from studying neuro, scientists actually know very little about the brain, Wade said. Luckily, wading into the unknown is Wades speciality.

I love how frequently we arrive at points in class where the professor stands in front of us and says We honestly do not know, Wade said.

One activity that allows Wade to dig into her not-yet-realized interests is her role as program coordinator for Alumni Breakfast, where she invites speakers from different backgrounds to speak about the work they do.

We call it existential crisis Tuesday, Wade said. Because a lot of speakers come in with cool professions Ive never heard of. And I just say Oh no, am I gonna go into that field now?

I attended an Alumni Breakfast with Wade on a damp Tuesday morning in February. Even though it was 8 a.m. and the speaker had a job in engineering, one of the few fields Wade hasnt touched, she diligently scrawled away at her notes as he spoke, blue eyes sparkling with passion.

A couple years ago, one speaker in particular grabbed her attention. Jennie Dorris has done research at Carnegie Mellon University studying how patients with Alzheimer's and dementia reacted to certain stimuli namely exercise, art and music.

Arts and neuroscience put together! Wade said. It was my dream.

Arts and neuroscience put together is exactly what Wade does in her lab now. Shes an undergraduate research assistant in the department of neuroscience, studying the limbic system a set of structures in the brain that deal with emotion and memory in mice and humans.

Wade is part of the mouse team, and she specifically studies a cluster of cells near the amygdala to try to understand neurodevelopment in areas of the brain involved with emotional processing. To observe the cells, Wade and her colleagues stain mouse brain tissue with a plethora of different colors.

[The images] look like space, she said. I love it.

But despite Wades love for neuroscience, her first job actually had nothing to do with brains at all. As an Americorps member during the summers before her first two years of college, she mentored 30 low-income inner city students. The project shes most proud of was when she taught them about the dangers of climate change and what they could do to curb its effects.

We taught them the little things like Turn off the lights when youre not using them, Wade said. But we also had them memorize the greenhouse gases. I watched a lot of them educate their parents about greenhouse gases, actually.

Having grown up in a small town in Massachusetts and attending a Catholic school, Wade said a lot of the lessons werent as progressive or inclusive as they could have been. It wasnt until she attended a social justice camp the summer after her senior year of high school that she began to learn about intersectionality and the concept of privilege, which she tries to recognize in herself and use to lift up others.

Thats actually how I got interested in food policy. I learned about food deserts at camp, Wade said. How are people able to stay healthy if they dont even have access to healthy food?

Shelly Danko+Day, a food policy expert in the Department of City Planning, said interdisciplinary expertise could bring an interesting spin to the topic of food insecurity, a project for which she was actively recruiting interns two years ago.

This brought Wade, a Pitt student with a double major in neuroscience and urban studies, into her office.

I just immediately thought Wow, shes great, Danko+Day said. She presented a lot of ideas integrating her studies in neuroscience and urban planning with food policy I was so impressed. I remember assuming she was in grad school.

In her interview with Danko+Day, Wade emphasized the need to view the issue from a personal perspective. It was an idea Danko+Day had never heard before, she said, but Wade took the project and ran with it.

Over the course of a semester she fished out data from the health department and layered it with rates of food insecurity by district, then compiled everything into eight separate reports.

Most people tend to focus solely on the data when doing a quantitative analysis, Danko+Day said, but Wade actually viewed each data point as a person, and wanted to paint a picture of every individual she described in her graphs and charts.

When you talk about health and health access, its very important to realize there are real people youre talking about, feeling the effects of a certain policy, Wade said.

Wade lights up I love connecting with people, she says. But connecting with people has proven a lot easier than connecting all of her passions into a career path. Last year, after spending two hours rifling through all of her life accomplishments, I asked Wade what the future looked like.

That question haunts me, she said at the time.

This year, before packing up my things and shrugging on my coat, I ask her that question again. Wade furrows her brow and tucks a strand of curly red hair behind her ear. She definitely wants to explore neuroscience research, she says, and shell probably go to graduate school. But other than that, shes not completely sure.

She pauses, allowing herself a relaxed smile.

The simple truth is, Im not sure where Ill end up, Wade said. But I am excited for the work Ill do as I figure it out.

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Kirsten Wade: Wading into the unknown - University of Pittsburgh The Pitt News

Neuroscience

Class of 2020, COVID-19 and sports: Track season ends before Susy Meza beats her own best time – Reno Gazette Journal

Susy Mesa, on far left, runs in a track meet for Sparks High, during her junior year. This year's season was cut short as schools stay closed amid the coronavirus pandemic.(Photo: Provided by Susy Meza)

Susy's story: This is the second series of stories following Sparks High School senior Susy Meza. Susy, 17, will graduate in June. She is the student body president, played sports and was on the prom committee. Sheplans to study neuroscience at the University of Nevada, Reno in the fall. The next few months of high school weresupposed to be the culmination of all her hard work, and the chance to beat her own record in the 300 meter hurdles before life was interrupted by the coronavirus pandemic.

Susy Meza keeps a picture of a post it note on herphone.

On it she had written oneof her senior year goals.

"I'm going to beat my personal record in hurdles," she said.

Story 1: Susy Mesa talks about missing her senior prom.

Susy, 17, runs track for Sparks High School. It's just one of the three sports Suzyhas done in high school. She was team captain this year for two, including the school's tennis team and cheerleading squad.

But beating the one-minute mark in the 300 meter hurdles was at the top of her high school bucket list.

Susy Meza, center, leads a chant. The high school senior's won't finish her last season of sports as schools remain closed amid the coronavirus pandemic.(Photo: Provided by Susy Meza)

And as a senior, she would lead the team in stretches before practice every day after school.

Instead, spring sports are canceled in Nevadaand across the country amid the coronavirus pandemic.

"I'm not really competitive but I wanted to grow and get better," Susy said of a senior year of missed track meets. "A lot of people run it faster than I do so I just wanted to do better for myself."

She will study neuroscience at the University of Nevada, Reno in the fall and wants to be a doctor.

This track season was likely the last time she would do competitive sports.

Susy Mesa plays tennis for Sparks High. Susy, 17, played three sports for Sparks High but the track season was cut short amid the COVID-19 pandemic.(Photo: Provided by Susy Mesa)

And she would be awarded the Golden Spike, a cord she could wear over her graduation gown to honor her for playing three sportsfor all four years of high school.

She would have been given the honor at thehigh school's now-canceled spring awards banquet.

She would have been the only one in hersenior class of more than 300 to get the honor this year.

"I don't know what happens now," she said. "I just know I have loved hurdles. It's about perseverance."

Susy Mesa, second from left, poses with her cheer team. Susy, 17, was the captain of the cheer, tennis and track team her senior year, now cut short, at Sparks High.(Photo: PRovided by Susy Mesa)

Siobhan McAndrew tells stories about the people of Northern Nevada and covers education in Washoe County. Read her journalism right here. Consider supporting her work by subscribing to the Reno Gazette Journal.

Read or Share this story: https://www.rgj.com/story/news/2020/04/13/covid-19-sparks-high-senior-susy-meza-miss-her-last-track-season/2948018001/

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Class of 2020, COVID-19 and sports: Track season ends before Susy Meza beats her own best time - Reno Gazette Journal

Neuroscience

Ed School Professor Kurt W. Fischer, a Champion of Kindness, Dies at 76 | News – Harvard Crimson

Jane T. Haltiwanger Fischer fell in love with her husband, Kurt W. Fischer, for his mind.

He was a brilliant, brilliant man, she said. I fell in love with him for his mind, but as the years went by, and certainly in the last years, it was very clear that what I loved the most about him was his heart.

Fischer was a professor at Harvards Graduate School of Education and the director of its Mind, Brain, and Education Program prior to his retirement in 2015. He died on March 30 at the age of 76. His cause of death remains unclear; he had Alzheimers disease and had come into contact with a staff member at his care facility who tested positive for COVID-19.

Fischer spent 27 years of his career at the Graduate School of Education.

One of his most notable academic accomplishments was integrating concepts from neuroscience and psychology with the study of education, creating a field he later called Mind, Brain, and Education.

Howard E. Gardner '65, a professor at the Graduate School of Education and longtime friend and colleague, said the idea to connect the three fields made Fischer a visionary.

Not only was that unique at Harvard, it was really unique in the world, Gardner said. There was nobody else yet who had coupled this stuff together.

Fischer also created the dynamic skill theory, a scale to analyze the complex manner in which humans construct knowledge and develop skills, depending on individual factors like mood, age, previous experience, and environmental factors, like level of support.

Mary Helen Immordino-Yang, who studied under Fischer and is now a professor at the University of Southern California, said that after founding the interdisciplinary field of Mind, Brain, and Education, dynamic skill theory is his most powerful legacy.

Rather than trying to reduce the complexities of human beings to statistics or simple averages, or group level metrics that are sometimes true on the whole, Kurt developed ways to appreciate the systematicity in the variation, Immordino-Yang said.

In addition to his theoretical work, Fischer was a proponent of expanding access to educational research for teachers and administrators. In 2006, Fischer helped develop the Usable Knowledge Program, a digital publication of education research that allows professionals to connect research to practice, according to its website.

Seth Fischer, his son, recently read through much of his fathers work, searching for the common theme.

I think that the through-line was that he wanted people to understand that children matter. Their circumstances matter. Listening to them matters. Their emotions matter, he said.

Dean of the Graduate School of Education Bridget Terry Long lauded Fischers lasting legacy as a cognitive psychologist in a remembrance published by the school.

From spearheading programming in neuroscience and education to his steadfast commitment to his students, we are a better community due to his influence and contributions, Long said.

Graduate School of Education lecturer Joseph Blatt said Fischer, for all his accomplishments, always remained generous and gentle.

Generous in the sense that he was always willing to do the extra bit to support me as a colleague, Blatt said. And gentle in that he always did it in a collegial and friendly way, not in a dictatorial way that he could have done as a tenured professor holding an endowed chair.

On top of his academic contributions, Fischers colleagues praised his patience and skill as a teacher and mentor.

He was very good with students whether they were brilliant and didn't need any help at all, or whether they had real learning challenges, Gardner said. He attracted, over the years, hundreds and hundreds of students who wanted to understand more about how to help kids.

Bryan Mascio was one of those students. Prior to his time at Harvard, he had worked as a teacher with students who struggled in traditional classrooms. Mascio said he felt out of place at Harvard until he worked with Fischer.

I honestly didn't feel like I really fit in. But Kurt made it very clear that that didn't mean that I didn't belong, Mascio said. He was very much embracing of teachers and the experience and the expertise that we bring to the table.

Like Mascio, Vanessa Rodriguez was a teacher before she came to Harvard. She was not originally in Fischers program, but after she explained her teaching philosophy to him, he invited her to study Mind, Brain, and Behavior.

He said to me, You're in the wrong program. You belong here, Rodriguez said. That was really powerful for me. As a Latina, it's not something anyone ever says to you.

At first, she was skeptical.

I said to him, No, I don't. I don't know anything about the mind, I don't know anything about the brain. I'm just a teacher, Rodriguez recalled. And he said to me, Of course you know about the mind and brain because you're a teacher. That's what you're an expert in.

Rodriguez and David B. Daniel, a professor at James Madison University, both said Fischer advocated for academics from underrepresented backgrounds.

He invited me to be a visiting scholar at Harvard. And in my mind, people like me just didn't ever get that opportunity. He gave me an opportunity, Daniel said.

Fischers mentorship was not limited to students and colleagues at Harvard. Students from across the world sought his guidance, and he readily gave it.

He was just the kindest, most generous, Daniel said. He gave his time to his students. And all these people in the field from all over the world who would just reach out to him and instead of blowing them off, he took an interest in them.

Seth Fischer said his father simply loved to help people.

He would want to help people, not because he thought he would get something out of it in the end. Not because he was trying to play some game of chess. Because he really just loved helping people, Seth Fischer said.

Kurt Fischer helped those around him through his humor, too.

When he was a graduate student at Harvard in the 1960s, one of his professors jokingly challenged his students to adopt a Rhesus monkey and take notes on its life. Fischer took him up on it.

He wanted to name it Frodo. But then he figured out that she was a woman, a girl, so he changed her name to Frodi, Seth Fischer said. He took care of it for as long as he safely could, raising her kind of as his child in graduate school, taking her everywhere with him, even once to Grand Central Station in New York.

Everyone around campus knew about Frodi and enjoyed Fischers whimsy, according to Gardner, who went to graduate school with Fischer.

Above all else, Seth Fischer called his father a champion of kindness.

In his work, in his family, that was sort of his core guiding principle, he said. He just also just loved ideas so much.

In the end, Fischer had more ideas than he had time to see through in his lifetime.

I know that he had more work that he wanted to do when he became ill and couldn't continue, Haltiwanger Fischer, his wife, said. That was very hard on him, but he also had very strong faith that his students are going to carry on.

His students did, in fact, carry on. Today, Mascio is a teacher educator and instructs his students on Fischers theories. Rodriguez is set to publish a major study on teacher wellbeing.

I'm using Kurt's legacy. It's all grounded in dynamic skill theory, Rodriguez said. And that's all based on the confidence and love and support and just undying belief in me that Kurt gave me.

Still, Seth Fisher wishes his father were around to see his legacy for himself.

He was just full of life and excitement about ideas and life and loving people. And I just feel like the world could really use him right now, he said.

Staff writer Camille G. Caldera can be reached at camille.caldera@thecrimson.com. Follow her on Twitter @camille_caldera.

Staff writer Kavya M. Shah can be reached at kavya.shah@thecrimson.com.

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Ed School Professor Kurt W. Fischer, a Champion of Kindness, Dies at 76 | News - Harvard Crimson

Neuroscience

Brown, Harvard, Yale. Pawtucket teen has been accepted to all 3, and more – The Providence Journal

PAWTUCKET The first acceptance letter came from Brown University. The next one from Harvard. When a thick envelope arrived from Yale University, Victoria Wijerathnayapa was totally blown away.

Wijerathnayapa is not only the first student from Blackstone Valley Prep to get into Harvard and Yale, she is the first one to be admitted to three Ivy League institutions.

Her first reaction?

"I was super happy," Wijerathnayapa said Thursday. "It was a really emotional experience, but a happy one."

The good news doesnt stop there. She was accepted at eight other colleges, including Brandeis, Swarthmore, Wellesley, Williams and Worcester Polytechnic Institute.

A first-generation college student whose mother is from Sri Lanka, Wijerathnayapa is not one to brag. She acknowledges that she doesnt fit the typical Ivy League mold. She didnt study abroad or attend a prestigious public or private school. In fact, shes never left New England.

She attributes her success to Blackstone Valley Prep, a cluster of charter schools in northern Rhode Island where college banners adorn classroom doors, where race and equity are part of the fabric of conversation.

In her Pawtucket elementary school, Wijerathnayapa says, she felt singled out for being bright.

In fifth grade, Wijerathnayapa won the lottery, literally. She was admitted to BVP, where her fortunes brightened.

"At BVP, my hard work and determination were not credited to my race but rather to my character," she said. "People here accepted me for who I was, not what I looked like."

Blackstone Valley Prep did more than encourage her academic brilliance. It allowed her to choose from a palette of enriching experiences, from attending a summer program at Brown University to taking a years worth of college classes at the Community College of Rhode Island, where she is currently taking cellular biology, English composition and public speaking.

At BVP, Wijerathnayapa said, she feels known. She ticked off the teachers who have been friends and mentors: Mr. Leger, her chemistry teacher and track coach; and Mr. Jose, one of her college and career counselors.

"Just this morning, I was stressed out about having to apply for scholarships, and online learning. So many things were coming at me," she said. "Being a first-generation student, not knowing how to navigate the system, I reached out to Ashley Gemma, my college counselor. We discussed how to arrange my time better. She helped me figure out what the next steps were."

Although she and her younger brother were born here, Wijerathnayapa still sees the world through an immigrants eyes, her mothers eyes.

"She sacrificed herself. She tells me theyve all been worth it."

Sri Lanka, a tropical island off the coast of India, was wracked by civil war for 26 years, from 1983 to 2009. In 2004, a typhoon killed some 30,000 residents.

"My mom is the rock in my life," she said. "Ever since I was born, she was pushing me to take advantage of all of the opportunities life gives you. I am eternally grateful to her."

A trip to the Museum of Science in Boston triggered Wijerathnayapas interest in neuroscience, her likely major in college. But an internship with the Rhode Island Board of Elections in eighth grade sent her in a separate direction: political science.

"I realized that youth voter apathy is a big problem," she said.

David Jose, the dean of BVPs college and careers, recalled how Wijerathnayapa walked around the cafeteria, imploring students to register to vote. Then she managed to get actual voting machines to the school for a student council election.

"She has so many interests," Jose said. "You could talk to her for hours about neuroscience and psychology. And you could talk to her for many hours about philosophy and political science."

Jose felt Wijerathnayapa was destined to have her choice of the most selective colleges. But he said getting admitted to an Ivy League school wasn't what motivated her.

"Her first goal was to learn as much as possible," Jose said. "That ethos drove her regardless. Nobody gets into three Ivies."

Her mother, he said, is her core influence.

"Her mom is a big cheerleader," he said. "But Victoria is also very connected to the Sri Lankan community. Its important for her to represent as much as possible the immigrant community. In a conversation we had the other day, she was asking, "What can I do to give back?"

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Brown, Harvard, Yale. Pawtucket teen has been accepted to all 3, and more - The Providence Journal

Neuroscience

Large-scale analysis links glucose metabolism proteins in the brain to Alzheimer’s disease biology – National Institute on Aging

In the largest study to date of proteins related to Alzheimers disease, a team of researchers has identified disease-specific proteins and biological processes that could be developed into both new treatment targets and fluid biomarkers. The findings suggest that sets of proteins that regulate glucose metabolism, together with proteins related to a protective role of astrocytes and microglia the brains support cells are strongly associated with Alzheimers pathology and cognitive impairment.

The study, part of the Accelerating Medicines Partnership for Alzheimers Disease (AMP-AD), involved measuring the levels and analyzing the expression patterns of more than 3,000 proteins in a large number of brain and cerebrospinal fluid samples collected at multiple research centers across the United States. This research was funded by the National Institutes of Healths National Institute on Aging (NIA) and published April 13 in Nature Medicine.

This is an example of how the collaborative, open science platform of AMP-AD is creating a pipeline of discovery for new approaches to diagnosis, treatment and prevention of Alzheimers disease, said NIA Director Richard J. Hodes, M.D. This study exemplifies how research can be accelerated when multiple research groups share their biological samples and data resources.

The research team, led by Erik C.B. Johnson, M.D., Ph.D, Nicholas T. Seyfried, Ph.D., and Allan Levey, M.D., Ph.D., all at the Emory School of Medicine, Atlanta, analyzed patterns of protein expression in more than 2,000 human brain and nearly 400 cerebrospinal fluid samples from both healthy people and those with Alzheimers disease. The papers authors, which included Madhav Thambisetty, M.D., Ph.D., investigator and chief of the Clinical and Translational Neuroscience Section in the NIAs Laboratory of Behavioral Neuroscience, identified groups (or modules) of proteins that reflect biological processes in the brain.

The researchers then analyzed how the protein modules relate to various pathologic and clinical features of Alzheimers and other neurodegenerative disorders. They saw changes in proteins related to glucose metabolism and an anti-inflammatory response in glial cells in brain samples from both people with Alzheimers as well as in samples from individuals with documented brain pathology who were cognitively normal. This suggests, the researchers noted, that the anti-inflammatory processes designed to protect nerve cells may have been activated in response to the disease.

The researchers also set out to reproduce the findings in cerebrospinal fluid. The team found that, just like with brain tissue, the proteins involved in the way cells extract energy from glucose are increased in the spinal fluid from people with Alzheimers. Many of these proteins were also elevated in people with preclinical Alzheimers, i.e., individuals with brain pathology but without symptoms of cognitive decline. Importantly, the glucose metabolism/glial protein module was populated with proteins known to be genetic risk factors for Alzheimers, suggesting that the biological processes reflected by these protein families are involved in the actual disease process.

Weve been studying the possible links between abnormalities in the way the brain metabolizes glucose and Alzheimers-related changes for a while now, Thambisetty said. The latest analysis suggests that these proteins may also have potential as fluid biomarkers to detect the presence of early disease.

In a previous study, Thambisetty and colleagues, in collaboration with the Emory researchers, found a connection between abnormalities in how the brain breaks down glucose and the amount of the signature amyloid plaques and tangles in the brain, as well as the onset of symptoms such as problems with memory.

This large, comparative proteomic study points to massive changes across many biological processes in Alzheimers and offers new insights into the role of brain energy metabolism and neuroinflammation in the disease process, said Suzana Petanceska, Ph.D., program director at NIA overseeing the AMP-AD Target Discovery Program. The data and analyses from this study has already been made available to the research community and can be used as a rich source of new targets for the treatment and prevention of Alzheimers or serve as the foundation for developing fluid biomarkers.

Brain tissue samples came from autopsy of participants in Alzheimers disease research centers and several epidemiologic studies across the country, including the Baltimore Longitudinal Study of Aging (BLSA), Religious Orders Study (ROS) and Memory and Aging Project (MAP), and Adult Changes in Thought (ACT) initiatives. The brain collections also contained samples from individuals with six other neurodegenerative disorders as well as samples representing normal aging, which enabled the discovery of molecular signatures specific for Alzheimers. Cerebrospinal fluid samples were collected from study participants at the Emory Goizueta Alzheimers Disease Research Center. These and other datasets are available to the research community through the AD Knowledge Portal, the data repository for the AMP-AD Target Discovery Program, and other NIA supported team-science projects operating under open science principles.

This press release describes a basic research finding. Basic research increases our understanding of human behavior and biology, which is foundational to advancing new and better ways to prevent, diagnose, and treat disease. Science is an unpredictable and incremental process each research advance builds on past discoveries, often in unexpected ways. Most clinical advances would not be possible without the knowledge of fundamental basic research.

The research in this study is funded by NIH grants R01AG053960, R01AG057911, R01AG061800, RF1AG057471, RF1AG057470, R01AG061800, R01AG057911, R01AG057339, U01AG061357, P50AG025688, RF1AG057470, RF1AG051633, P30AG10161, R01AG15819, R01AG17917, U01AG61356, R01AG056533, K08NS099474, U01AG046170, RF1AG054014, RF1AG057440, R01AG057907, U01AG052411, P30AG10124, U01AG046161, R01AG050631, R01AG053960, R01AG057339, U01AG061357, P50AG005146, U24NS072026, and P30AG19610.

Reference: Johnson ECB et al. Large-scale proteomic analysis of Alzheimers disease brain and cerebrospinal fluid reveals early changes in energy metabolism associated with microglia and astrocyte activation. Nature Medicine. 2020 Apr 13. doi:10.1038/s41591-020-0815-6

About the National Institute on Aging (NIA): NIA leads the U.S. federal government effort to conduct and support research on aging and the health and well-being of older people. Learn more about age-related cognitive change and neurodegenerative diseases via NIAs Alzheimer's and related Dementias Education and Referral (ADEAR) Center website. For information about a broad range of aging topics, visit the main NIA website and stay connected.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit the NIH website.

NIH...Turning Discovery Into Health

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Large-scale analysis links glucose metabolism proteins in the brain to Alzheimer's disease biology - National Institute on Aging

Neuroscience

Brain Discovery Could Have Important Implications for Neurodegenerative Diseases – University of Virginia

Improper removal of faulty brain cells during neurodevelopment may cause lifelong behavioral issues, new research from the University of Virginia School of Medicine suggests. The finding also could have important implications for a wide range of neurodegenerative diseases, such as Alzheimers and Parkinsons diseases.

UVA neuroscientists have discovered that an unexpected form of cellular cleanup takes place in developing brains. If this process goes wrong happening too little or too much it can cause permanent changes in the brains wiring. In lab mice, this results in anxiety-like behavior, and it may play a role in neurological conditions such as autism in humans.

You dont want [brain] cells to have genomic compromises. You dont want damaged DNA. So, this would be a normal mechanism to expel those cells from being incorporated into the central nervous system, researcher Catherine R. Lammert explained. When the damage isnt recognized, the cells that have DNA damage live on in the [central nervous system] and can be seen by accumulation of DNA damage in the brain.

The cellular cleaner the researchers spotted, the AIM2 inflammasome, has been associated primarily with the bodys immune response to infections, but has not been extensively studied in the brain. But there it plays a critical role in ensuring the developing brain is assembled properly and functions correctly, Lammert discovered in collaboration with principal investigator John Lukens.

Neurodevelopment is a very complicated process, said Lammert, a graduate student whose specialized skills were instrumental in the discovery. This form of cell death actually plays a role in removing unwanted cells from the brain to establish a healthy [central nervous system] with the correct connections and the right number of cells.

More than half the neurons created during brain development end up dying, so proper cleanup is essential, noted Lukens, of UVAs Department of Neuroscience. Too much or too little is thought to underlie everything from autism to intellectual disability any type of neurodevelopmental disorder, he said.

For example, ataxia is a condition that causes people to lose control of their movements. Theres a potential that this pathway could be contributing to the neuronal loss that is seen in ataxia, said Lukens, a researcher with UVAs Center for Brain Immunology and Glia, or BIG. On the one hand, you need it [the cleanup], but if you have too much of it, it can have negative consequences, like, potentially, ataxia. A lot of the early-onset neurodegenerative diseases are associated with mutations in DNA damage repair proteins, and this pathway could also be involved.

The discovery came about somewhat serendipitously, the result of an observation of the behavior of lab mice while the researchers were investigating traumatic brain injury. But following that unexpected lead has given scientists a better understanding of brain development, and that understanding may one day yield new treatments for neurological diseases.

Lukens, a member of UVAs Carter Immunology Center, cautioned that such treatments are likely a long way off, but he said a therapy based on the discovery might have widespread applications.

Hitting this pathway in the mature brain would likely provide a treatment strategy for any neurodegenerative disease associated with DNA damage, he said. And thats all the major heavy hitters: Alzheimers disease, Parkinsons, ALS.

The researchers havepublished their findings in the prestigious journal Nature. The studys authors were Lammert, Elizabeth L. Frost, Calli E. Bellinger, Ashley C. Bolte, Celia A. McKee, Mariah E. Hurt, Matt J. Paysour, Hannah E. Ennerfelt and Lukens.

The research was supported by the Hartwell Foundation; Rettsyndrome.org grant 22349; the Owens Family Foundation; and Brain & Behavior Research Foundation grant 27515. Lammert was supported by a predoctoral training grant from the National Institutes of Healths National Institute of General Medical Sciences and a Wagner Fellowship.

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Neuroscience

Event Cells in the Brain Help Organize Memory into Meaningful Segments – Scientific American

Our recollection of events is usually not like a replay of digital video from a security cameraa passive observation that faithfully reconstructs the spatial and sensory details of everything that happened. More often memory segments what we experience into a string of discrete, connected events. For instance, you might remember that you went for a walk before lunch at a given time last week without recalling the soda bottle strewn on the sidewalk, the crow cawing in the oak tree in your yard or the chicken salad sandwich you ate upon your return. Your mind designates a mental basket for walk and a subsequent bin for lunch that, once accessed, make many of these finer details available. This arrangement raises the question of how the brain performs such categorization.

A new study by neuroscientist Susumu Tonegawa of the Massachusetts Institute of Technology and his colleagues claims to have discovered the neural processing that makes this organization of memory into discrete units possible. The work has implications for understanding how humans generalize knowledge, and it could aid efforts to develop AI systems that learn faster.

A brain region called the hippocampus is critical for memory formation and also seems to be involved in navigation. Neurons in the hippocampus called place cells selectively respond to being in specific locations, forming a cognitive map of the environment. Such spatial information is clearly important for episodic (autobiographical rather than factual) memory. But so, too, are other aspects of experience, such as changing sensory input. There is evidence that neurons in the hippocampus encode sensory changes by altering the frequency at which they fire, a phenomenon termed rate remapping. According to research by neuroscientist Loren Frank of the University of California, San Francisco, and his colleagues, such changes may also encode information about where an animal has been and where it is going, enabling rate remapping to represent trajectories of travel.

Besides coding continuously changing variables, whether sensory inputs or route trajectories, some imaging studies previously suggested that the brain also processes experience as segmented events. But exactly how it achieves this process at a neural level was not known. In the new study, published last week in Nature Neuroscience, the teamled by Chen Sun, a graduate student in Tonegawas labdevised a task that attempted to disentangle the discrete, segmented nature of events from the continuously changing spatial and sensory details of moment-to-moment experience. The researchers trained mice to run around a square track. After doing four laps, the animals were rewarded with a sweet treat. They visited the reward box after every lap, segmenting each trial into four events (with the reward defining the end of a trial). Each lap traversed the same route, so sensory and location information was constant from one event to the next, allowing the researchers to attribute brain activity differences to what did change: the laps, or events.

The researchers recorded activity in hundreds of hippocampal cells while the mice performed this task and found that around 30 percent of cells showed a lap-specific pattern. Some of them were highly active when a rodent ran through the location it responded to on the first lap and relatively quiet during the remaining three laps. Others responded on the second lap far more than the rest, and so on. These neurons, which the researchers termed event-specific rate remapping, or ESR, cells, seemed to signal which lap a mouse was on.

To confirm the ESR cells were really encoding events, the researchers conducted experiments using tracks that were elongated along one dimension, increasing their length. Even when lap length was randomly altered between trials, the cells were still much more active on their preferred lap, showing the activity could not be related to the time elapsed or distance travelled. The results support the idea that the hippocampus can express representations of relevant variables, including, in this case, the number of laps since a reward was delivered, says Frank, who was not involved in the study.

In another experiment, the team trained mice on a square track on the first day, then substituted a circular track on the next one. Shifting to a new environment resulted in the ESR cells spatial responses being completely remapped onto the circular track. Strikingly, though, the lap that those neurons preferentially responded to remained the same. These findings suggest that ESR activity represents segmented units of experienceand that this event code can be transferred between different experiences that share a common structure.

Tonegawa compares this process to a familiar scenario. If you go to a restaurant to have dinner with your friend, that episode is made up of different segments: you arrive at the restaurant, then order an appetizer, then you choose a main dish, and then, usually, you have dessert, he says. As all this is going on, the stimuli coming to you are changing. But at the same time, its made up with distinct events, where you switch from the appetizer, to eating a main dish, dessert, and so on. The coding revealed in the study may explain how the brain abstracts events such as main course across different visits to different restaurants with different friends. And this idea may offer insight into how the brain generalizes knowledge to learn efficiently. Youre transferring knowledge you already have, based on past experience, to learn new things, Tonegawa says. Thats why we can learn things much faster. These insights, he thinks, could help engineers develop AI systems with the ability to transfer competencies from one environment to another, such as for medical robots moved between hospitals.

The circular track experiment showed that brain responses that specify your precise location can be altered without affecting event-specific activity. In a final experiment, the team asked whether the reverse is also true. A region called the medial entorhinal cortex (MEC) works closely with the hippocampus in spatial cognition and navigation. There is also evidence that it is involved in segmenting experience into sequential events. The researchers used optogenetics (a technique involving genetically altering cells so they can be activated or inhibited using light) to switch off signals from the MEC to the hippocampus while mice performed the running task. Doing so had no effect on location-specific responses but completely disrupted lap-specific ones, suggesting place and event encoding can be separately manipulatedeven though the same cells process both aspects of experience.

One limitation of the study is that running repeatedly around a track is unlike most natural experiences. Theres no demonstration that these event-related patterns exist the first time an animal experiences a set of eventsonly that they appear after many repeats of a now familiar sequence, Frank says. This is not really the same as our episodic memories, where each new experience gets encoded separately and stored as an event the first (and often only) time it happens. He thinks the cells represent well-learned and relevant elements of an experience with repeating elements. That arrangement, he says, is reminiscent of reports from studies of hippocampal neurons that fire similarly, but not identically, in geometrically repeated elements of the same environment.

This is an insightful experiment, performed with the care and numerous controls characteristic of Tonegawas lab, says neuroscientist Gyrgy Buzski of the NYU Grossman School of Medicine, who was not involved with the study, though he provided comments to the researchers. But Buzski has a more radical take on what is happening. He thinks all of the properties researchers have assigned to hippocampal neurons are different aspects of the same fundamental mechanism. To explain this idea, he compares it to the relationship between the motion of a vehicles engine and its distance travelled and journey time different variables reflecting a single underlying process.

In the case of episodic memory, the hypothesized elements are what, where and when. The definition of episodic memory is: What happened to me, where and when? Buzski says. When you combine these elements, it re-creates the event. This is called memory, he adds. Researchers relate the activity they observe to what, where or when, but all the hippocampus is doing is efficiently encoding experience into a neuronal sequence. The hippocampus is like a librarian that tells you to go to shelf five, row two. Then the next book is this, then this, and so on, he says. But the librarian is blind to the content of these sequences, which is constructed in the cortex. Thus, Buzskis interpretation of the new findings is that cells do not encode abstract event-specific propertiessuch as which lap number or dinner course one is experiencingso much as they generate the ordinal sequences that give memory the order necessary for us to make sense of it.

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Neuroscience

AI researchers hope to ID healthcare workers with COVID-19 before they show symptoms – AI in Healthcare

The goal is to ultimately detect when providers are infected with the virus as quickly as possible, limiting their ability to potentially spread COVID-19 to their colleagues, patients and loved ones back home.

We are continuously monitoring the mind-body connectivity through our integrated neuroscience platform measuring the autonomic nervous system, fatigue, anxiety, circadian rhythms, and other human resilience and recovery functions, Ali Rezai, MD, executive chair of the WVU Rockefeller Neuroscience Institute, said in a prepared statement. Our AI-driven models are currently predicting symptoms 24 hours prior to onset, and we are working toward a three-plus day forecast. This forecasting capability will help us get ahead of this pandemic; limit the spread to protect healthcare workers, their families, and our communities; and improve our understanding of health recovery.

At Oura, weve heard firsthand from our users how the physiological signals tracked by the ring have predicted the onset of the virus before other symptoms manifest, Harpreet Rai, CEO of Oura Health, said in the same statement. Were grateful we can apply this knowledge to help vulnerable caregivers swiftly identify the earliest signs of the disease, and take the appropriate protective measures to limit its spread.

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AI researchers hope to ID healthcare workers with COVID-19 before they show symptoms - AI in Healthcare

Neuroscience

How Stories Connect And Persuade Us: Unleashing The Brain Power Of Narrative – OPB News

When you listen to a story, your brain waves actually start to synchronize with those of the storyteller. And reading a narrative activates brain regions involved in deciphering or imagining a person's motives and perspective, research has found.

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When you listen to a story, whatever your age, youre transported mentally to another time and place and who couldnt use that rightnow?

We all know this delicious feeling of being swept into a story world, says Liz Neeley, who directs The Story Collider, a nonprofit production company that, in nonpandemic times, stages live events filled with personal stories about science. You forget about your surroundings, she says, and youre entirelyimmersed.

Depending on the story youre reading, watching or listening to, your palms may start to sweat, scientists find. Youll blink faster, and your heart might flutter or skip. Your facial expressions shift, and the muscles above your eyebrows will react to the words another sign that youreengaged.

A growing body of brain science offers even more insight into whats behind theseexperiences.

On functional MRI scans, many different areas of the brain light up when someone is listening to a narrative, Neeley says not only the networks involved in language processing, but other neural circuits, too. One study of listeners found that the brain networks that process emotions arising from sounds along with areas involved in movement were activated, especially during the emotional parts of thestory.

As you hear a story unfold, your brain waves actually start to synchronize with those of the storyteller, says Uri Hasson, professor of psychology and neuroscience at Princeton University. When he and his research team recorded the brain activity in two people as one person told a story and the other listened, they found that the greater the listeners comprehension, the more closely the brain wave patterns mirrored those of thestoryteller.

Brain regions that do complex information processing seem to be engaged, Hasson explains: Its as though, Im trying to make your brain similar to mine in areas that really capture the meaning, the situation, the schema the context of theworld.

Other scientists turned up interesting activity in the parts of the brain engaged in making predictions. When we read, brain networks involved in deciphering or imagining another persons motives, and the areas involved in guessing what will happen next are activated, Neeley says. Imagining what drives other people which feeds into our predictions helps us see a situation from different perspectives. It can even shift our core beliefs, Neeley says, when we come back out of the story world into regularlife.

Listeners, in turn, may keep thinking about the story and talk to others about it, she says, which reinforces the memory and, over time, can drive a broader change inattitudes.

Different formats of information lists of facts, say, or charts may be better suited to different situations, researchers say, but stories wield a particularly strong influence over our attitudes andbehavior.

In health care contexts, for example, people are more likely to change their lifestyles when they see a character they identify with making the same change, notes Melanie Green, a communication professor at the University at Buffalo who studies the power of narrative, including in doctor-patient communication. Anecdotes can make health advice personally important to a patient, she finds. When you hear or read about someone you identify with who has taken up meditation, for example, you might be more likely to stick with ityourself.

Stories can alter broader attitudes as well, Green says like our views on relationships, politics or the environment. Messages that feel like commands even good advice coming from a friend arent always received well. If you feel like youre being pushed into a corner, youre more likely to push back. But if someone tells you a story about the time they, too, had to end a painful relationship, for example, the information will likely come across less like a lecture and more like a personaltruth.

Neeley has been taking advantage of these effects to shift perceptions about science and scientists in her work with Story Collider. We try and take everybody all different people and perspectives put them onstage, and hear what a life in science is really like, shesays.

Solid information in any form is good, Green says. But thats not necessarily enough. A vivid, emotional story can give that extra push to make it feel more real or more important. If you look at the times somebodys beliefs have been changed, she says, its often because of a story that hits them in the heart.

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