News

Researchers Uncover Possible New Biomarker for Psychosis Diagnosis

Monday, November 25, 2024

The current standard of care for psychosis is a diagnostic interview, but what if it could be diagnosed before the first symptom emerged? Researchers at the Del Monte Institute for Neuroscience at the University of Rochester are pointing toward a potential biomarker in the brain that could lead to more timely interventions and personalized care.

“Establishing such biomarkers could provide a key step in changing how we care for, treat, and offer interventions to people with psychosis,” said Brian Keane, PhD, assistant professor of Psychiatry, Center for Visual Science, and Neuroscience at the University of Rochester Medical Center. Keane recently co-authored an article in Molecular Psychiatry that identifies how MRI scans could reveal brain differences in people with psychosis. “Aside from potentially predicting future psychosis onset, biomarkers could also help stratify patients into clinically meaningful subgroups and suggest new options for treatment or intervention.”

Using data collected by the Human Connectome Early Psychosis Project, researchers looked at MRI scans from 159 participants. These included 105 who developed a psychotic disorder up to five years prior to testing. In the brains of participants with psychosis, researchers found that sensory regions in the cortex were more weakly connected to each other and more strongly connected to the thalamus, the brain’s information relay station. These differences were confined to the somatomotor network, which processes bodily movement and sensations, and a visual network, which generates representations of objects, faces, and complex features. Combining the dysconnectivity patterns across these two networks allowed the researchers to create a “somato-visual” biomarker.

Previous research has suggested that abnormal brain connectivity exists prominently in the sensory networks of people with schizophrenia, but it remained unclear which networks were most responsible or whether dysconnectivity could be explained by other illness factors, such as antipsychotic use, anxiety, or stress.

“What makes this biomarker unique is its large effect size, its robustness to over a dozen common confounds, and its high reliability across multiple scans. A single five-minute scan could potentially improve our ability to predict which at-risk individuals will transition to a psychotic disorder, which in turn could allow for more timely treatments or interventions,” Keane said. “It also gives us a place to keep looking. An important next step will be to determine if the somato-visual biomarker emerges before or as psychosis begins.”

Additional authors include Yonatan Abrham, Boyang Hu, and Brent Johnson of the University of Rochester, Carrisa Cocuzza of Yale University, and Michael Cole of Rutgers University. This work was supported by a K01 grant and a Psychiatry Department pilot grant at the University of Rochester.

--Author: Kelsie Smith Hayduk

Nathan Smith Fills New Role at SMD: Associate Dean for Research Mentorship

Monday, November 4, 2024

As a PhD graduate and now principal investigator of a research lab at the University of Rochester School of Medicine and Dentistry (SMD), Nathan A. Smith, MS, PhD, understands the importance of mentorship and what it takes to set trainees up for success. He will use his experience on both sides of the coin—as a student and a faculty member—to guide his work as the inaugural associate dean for Research Mentorship at SMD.

In today’s fast-paced world of science, effective mentorship is increasingly important. Major funding agencies, including the National Institutes of Health and National Science Foundation, have made mentorship training a mandatory part of new grants. Rapidly evolving technologies, increased competition for funding and high-profile publications, and research misconduct and integrity concerns coalesce to create a complicated environment for students to navigate. Mentors and mentees need tools, training and practical guidance to chart a successful and fulfilling path in academia.

“Mentorship sounds simple, but it isn’t always easy or intuitive,” said Smith, associate professor of Neuroscience. “I’m excited to educate and empower our trainees and faculty members to put their best foot forward. No one has the perfect formula, but if we all have a seat at the table and work together, I’m confident we can create a mentoring culture where everyone thrives.”

In partnership with Sarah Peyre, EdD, SMD vice dean for education, and Rick Libby, PhD, senior associate dean for Graduate Education and Postdoctoral Affairs and interim vice provost and interim University dean of Graduate Education, Smith will develop policies, programs, and curriculum to help research faculty become more skilled mentors. He’ll also create and implement initiatives focused on learner growth and development, supporting graduate student and postdoctoral scholars’ career goals. With mentors and mentees from a wide range of backgrounds, Smith will infuse cultural humility and community building into all of these efforts.

How to Increase Attention Span

Thursday, October 31, 2024

Tips and tricks to stay focused for longer

Focus seems to be in short supply these days. We’re surrounded by multiple devices and tasks competing for our attention all the time, so it can be tricky to stay dialed in. But there are simple ways to improve attention span, says UR Medicine expert Ian Fiebelkorn.

Our brain uses filters to process information. These filters work to enhance the important information, while suppressing distracting information. This process is referred to as attention.

“Aspects of attention are sometimes compared to a spotlight that continuously scans the environment, pausing to illuminate important information,” Fiebelkorn explains.

For example, when crossing a street to meet a friend, you may be mostly focused on your friend standing on the other side of the road. Your attentional spotlight can focus on them but will also track other important events such as approaching vehicles.

“You could think of attention span as the amount of time until the attentional spotlight begins to dim,” adds Fiebelkorn.

The problem is, a constant flow of information from the outside world floods our brain. And because the brain has limited ways to process info, we can’t fully process everything at once. But we can use simple methods to increase a short attention span.

Comparing gene sequences across species to understand aging and dementia

Wednesday, October 16, 2024

A new grant partners longevity researchers and Alzheimer’s experts at Rochester to study the gene mechanisms that contribute to long and healthy lifespans

Whether you give a mouse a cookie, as the book title goes, or kale leaves, or hot-stone massages, they will not live longer than two to three years. But other mammals, like naked mole rats and bowhead whales, can live much longer—and perhaps can teach us to follow suit.

At the University of Rochester, a new collaboration between leading longevity researchers and brain disease experts examines gene mechanisms responsible for long life, drawing on the latest findings to pursue novel interventions for the treatment and prevention of Alzheimer’s disease and related dementias.

Today’s oldest naked mole rats, born during the Reagan administration, show exceptional resistance to age-related disease. Meanwhile, when degus (small Chilean rodents) develop Alzheimer’s disease, it progresses in a remarkably similar manner to humans. Examining the genes of these mammals has the potential to yield insights into how humans can live longer—with their cognitive faculties intact.

“No matter how much you pamper a mouse, it will not live to 40 years as naked mole rats will,” says Vera Gorbunova, the Doris Johns Cherry Professor in the departments of biology and of medicine. To bridge the knowledge gap from rodents, whales, and other long-lived mammals to humans, Gorbunova tapped M. Kerry O’Banion, a professor of neuroscience at the University of Rochester Medical Center, who has studied the pathogenesis of Alzheimer’s disease for 30 years.

Neuroimaging study reveals structural brain differences in children with autism - MSN News

Thursday, October 10, 2024

There is new evidence that the cells responsible for communication in the brain may be structured differently in children with autism. Researchers at the Del Monte Institute for Neuroscience at the University of Rochester discovered that in some areas of the brain neuron density varies in children with autism when compared to the general population.

“We are at the beginning of understanding the true impact that the extraordinary data collected by the ABCD Study will have on the health of our children,” says John Foxe, the Kilian J. and Caroline F. Schmitt Chair in Neuroscience and the director of the Del Monte Institute for Neuroscience and the Golisano Intellectual and Developmental Disabilities Institute. “It is truly transforming what we know about brain development as we follow this group of children from childhood into early adulthood.”

Research finds neurons look different in children with autism

Wednesday, October 9, 2024

Neuronal measurements may provide new insight into diagnosis & therapeutic interventions for autism

There is new evidence that the cells responsible for communication in the brain may be structured differently in children with autism. Researchers at the Del Monte Institute for Neuroscience at the University of Rochester discovered that in some areas of the brain neuron density varies in children with autism when compared to the general population.

“We've spent many years describing the larger characteristics of brain regions, such as thickness, volume, and curvature,” said Zachary Christensen, MD/PhD candidate at the University of Rochester School of Medicine and Dentistry, and first author of the paper out today in Autism Research. “However, newer techniques in the field of neuroimaging for characterizing cells using MRI, unveil new levels of complexity throughout development.”

Imaging provides new insight into brain development

Researchers used brain imaging data collected from more than 11,000 children ages 9-11. They compared the imaging of the 142 children in that group with autism, to the general population and found there was lower neuron density in regions of the cerebral cortex. Some of these regions of the brain are responsible for tasks like memory, learning, reasoning, and problem-solving. In contrast, the researchers also found other brain regions, such as the amygdala—an area responsible for emotions—that showed increased neuron density. In addition to comparing the scans of children with autism to those of children without any neurodevelopmental diagnosis, they also compared the children with autism to a large group of children diagnosed with common psychiatric disorders like ADHD and anxiety. The results were the same, suggesting that these differences are specific to Autism.

“People with a diagnosis of autism often have other things they have to deal with, such as anxiety, depression, and ADHD. But these findings mean we now have a new set of measurements that have shown unique promise in characterizing individuals with autism,” Christensen said. “If characterizing unique deviations in neuron structure in those with autism can be done reliably and with relative ease, that opens a lot of opportunities to characterize how autism develops, and these measures may be used to identify individuals with autism that could benefit from more specific therapeutic interventions.”

Turning brain cells on using the power of light

Thursday, October 3, 2024

University of Rochester researchers have demonstrated a noninvasive method using BL-OG, or bioluminescent optogenetics, that harnesses light to activate neurons in the brain. The ability to regulate brain activation could transform invasive procedures such as deep brain stimulation that are used to treat Parkinson’s disease and other neurological conditions.

The advantage of this new technique is that it can create brain activation without the use of an implanted device in the brain to deliver physical light, according to Manuel Gomez-Ramirez, an assistant professor of brain and cognitive sciences and with the University’s Del Monte Institute for Neuroscience, and the senior author of the study, which appears in the journal NeuroImage.

“BL-OG is an ideal method for noninvasively teasing apart neural circuits in the brain,” says Emily Murphy, the first author of the study and manager of the Haptics Lab, led by Gomez-Ramirez. “There are still so many things to learn about the structure and function of distinct brain areas and neuronal cell types that will help us understand how healthy brains function.”

A revolutionary map of the fly brain could transform neuroscience

Wednesday, October 2, 2024

Researchers have developed a groundbreaking new resource—theFlyWire Connectome, described today in the journal Nature—that maps every neuron and synaptic connection in the central brain of Drosophila melanogaster, or the fruit fly. Totaling over 130,000 neurons and 30 million synaptic connections, this revolutionary tool will expedite inquiry into how the brain works and expand the questions that can be asked.

“The importance of this cannot be understated, because it really just drastically changes the field,” said Gabriella Sterne, PhD, assistant professor of Biomedical Genetics and Neuroscience at the Del Monte Institute for Neuroscience at the University of Rochester, who contributed to this research as a member of the FlyWire consortium, a group co-led by the MRC Laboratory of Molecular Biology in Cambridge, United Kingdom, Princeton University, the University of Vermont, and the University of Cambridge. “The first time I saw the complexity of the connectome, it literally blew my mind because we have been thinking of these circuits in a simplistic manner, but we can now appreciate that they are far more complex than we imagined.”

Researchers will be able to use this resource to untangle complex brain connections and functions, accelerate findings, inform machine learning and artificial intelligence, and improve our understanding of the human brain. “The connectome makes it easier to uncover general and fundamental principles that govern neural circuit function. Discovering such principles in a relatively simple brain will inform the search for similar processes in the human brain, potentially leading to unifying theories of brain function,” Sterne explained. “Once we understand the computations that neural circuits are performing in a healthy brain, we can start to ask how circuit function is disrupted in disease.”

Read More: Watch Dr. Gabriella Stere, Ph.D. on Rochester First: How a map of a fruit fly’s brain could help unlock the mysteries of our own

John Foxe spoke on Fairport Central School District making changes to school day schedule

Wednesday, September 18, 2024

John Foxe, PhD, director of the Del Monte Institute for Neuroscience, spoke to WHAM (Sept. 18) about Fairport School District altering start times for middle and high schoolers in 2026. "We have clear evidence from neurosciences that it’s at night when you’re sleeping that your memory systems consolidate the information you took in during the day," said Foxe. "What we will see is less falling asleep, less distraction, better behavior, more learning and ability to take on more material.”

Celebrating Decades of Advances in Myotonic Dystrophy Research

Tuesday, September 17, 2024

On September 15, Strong Memorial Hospital lit up blue to commemorate Myotonic Dystrophy Awareness Day and the significant scientific progress achieved in Rochester and beyond over the past 30 years. These advancements have brought researchers closer than ever to developing treatments for this debilitating disease.

The recent renewal of a joint University of Rochester Medical Center (URMC) and University of Florida Paul D. Wellstone Muscular Dystrophy Cooperative Research Center will further strengthen these efforts. URMC, one of the original Wellstone Centers established in 2003, has been continuously funded by the National Institutes of Health to study myotonic dystrophy and facioscapulohumeral muscular dystrophy.

"The Wellstone Center program has been instrumental in our understanding of the molecular and physiological processes underlying the most common form of adult-onset muscular dystrophy, myotonic dystrophy," said Charles Thornton, MD, co-director of the Wellstone Center. "This knowledge has enabled us to develop promising treatments for this disease. The center's organization, which includes the National Registry for myotonic dystrophy, is built upon strong and longstanding collaborations between basic researchers at the University of Florida and clinical experts at the University of Rochester."

The new funding will support research in Rochester and Florida aimed at accelerating clinical research for novel gene therapies in myotonic dystrophy, type one (DM1), and prepare to translate these therapies into clinical practice, if approved. It is anticipated that modified versions of these therapies could also be effective for myotonic dystrophy, type two (DM2). To expedite clinical trials for DM2, researchers will expand their basic and clinical research efforts in this area.

Researchers at the University of Rochester Medical Center have been at the forefront of these advancements. Over three decades ago, Robert (Berch) Griggs, MD, Richard Moxley, MD, and Thornton were the first to describe myotonic dystrophy type 2. In collaboration with patients and families, the national registry has been an invaluable resource for understanding the natural history of the disease and conducting clinical research.

Cleaning up the aging brain

Thursday, August 15, 2024

Rochester scientists are restoring the brain’s trash disposal system with a drug currently used to induce labor

Alzheimer’s, Parkinson’s, and other neurological disorders can be seen as “dirty brain” diseases, where the brain struggles to clear out harmful waste. Aging is a key risk factor because, as we grow older, our brain’s ability to remove toxic buildup slows down. However, new research in mice demonstrates that it’s possible to reverse age-related effects and restore the brain’s waste-clearing process.

“This research shows that restoring cervical lymph vessel function can substantially rescue the slower removal of waste from the brain associated with age,” says Douglas Kelley, a professor of mechanical engineering at the University of Rochester. “Moreover, this was accomplished with a drug already being used clinically, offering a potential treatment strategy.”

Kelley is one of the lead authors of the study, which appears in the journal Nature Aging, along with Maiken Nedergaard, codirector the University’s Center for Translational Neuromedicine. The study is one of many collaborations carried out by researchers at Rochester’s Hajim School of Engineering & Applied Sciences and the Medical Center.

First described by Nedergaard and her colleagues in 2012, the glymphatic system is the brain’s unique waste removal process that uses cerebrospinal fluid (CSF) to wash away excess proteins generated by energy-hungry neurons and other cells in the brain during normal activity. The discovery pointed the way to potential new approaches to treat diseases commonly associated with the accumulation of protein waste in the brain, such as Alzheimer’s (beta amyloid and tau) and Parkinson’s (alpha-synuclein). In healthy and young brains, the glymphatic system does a good job of flushing away these toxic proteins; however, as we age, this system slows, setting the stage for these diseases.

Marissa Sobolewski: Nature, nurture, and neuroscience

Monday, August 12, 2024

How Uganda’s chimpanzees have shaped the assistant professor’s research journey

Marissa Sobolewski’s road to a scientific career began in Uganda’s Kibale National Park, home to one of the planet’s most diverse populations of primates and the filming location for the 2012 Disney nature documentary Chimpanzee and the 2023 Netflix series Chimp Empire. Learning to embrace scientific complexity while finding a community that values collaborative research has fueled Sobolewski’s drive to discover how the world around us impacts body and mind.

Starting her lab at the University of Rochester Medical Center in 2018, she is now an assistant professor of environmental medicine and of neuroscience as well as a member of the University’s Institute for Human Health and the Environment and the Intellectual and Developmental Disabilities Research Center. The Sobolewski Lab explores how the environment, including exposure to chemicals and other variables like stress, influences brain development and behavior. Studying how the environment influences molecular targets like hormones, epigenetic profiles, and neurotransmitter balance helps us better understand the environment’s role in conditions like ADHD and autism, ultimately improving risk assessment and protecting public health.

Connection speed in the brain may impact how people with autism process visual illusions

Monday, July 22, 2024

Visual illusions continue to provide clues to how the brain processes what people with autism see. New research suggests that connections in the brain that send information about the context of what is being seen may operate more slowly in people with autism. “In that case, it would make sense for the brain to focus more on the details of what we are seeing than on the big picture,” said Emily Knight, MD, PhD, assistant professor of Neuroscience and Pediatrics and first author of the study published in the Journal of Neurophysiology. “Some of the things we would like to explore next are how these changes in timing might relate to the sensory or repetitive behaviors that we often see in individuals on the autism spectrum.”

As a clinician scientist, Knight’s research informs her work with patients and their families. “It’s important to remember that the basic processing of what we see, hear, and touch forms the foundation for how we interact with our environment and people,” Knight said. “Learning about how the brains of children who are neurodiverse may truly be seeing the world in a different way helps me to better understand and support them in our community.”

Additional authors include senior author John Foxe, PhD, director of the Golisano Institute for Intellectual and Developmental Disabilities and the Del Monte Institute for Neuroscience and Edward Freedman, PhD, of the University of Rochester, Ted Altschuler, PhD, Sophie Molholm, PhD, and Jeremy Murphy of Albert Einstein College of Medicine. This research was supported by the National Institute of Mental Health, the Rose F. Kennedy Intellectual and Developmental Disabilities Research Center, the University of Rochester Intellectual and Developmental Disabilities Research Center, and University of Rochester Clinical and Translational Science Institute KL2 Career Development Award.

Study Reveals Brain Fluid Dynamics as Key to Migraine Mysteries, New Therapies

Friday, July 5, 2024

New research describes for the first time how a spreading wave of disruption and the flow of fluid in the brain triggers headaches, detailing the connection between the neurological symptoms associated with aura and the migraine that follows. The study also identifies new proteins that could be responsible for headaches and may serve as foundation for new migraine drugs.

“In this study, we describe the interaction between the central and peripheral nervous system brought about by increased concentrations of proteins released in the brain during an episode of spreading depolarization, a phenomenon responsible for the aura associated with migraines,” said Maiken Nedergaard, MD, DMSc, co-director of the University of Rochester Center for Translational Neuromedicine and lead author of the new study, which appears in the journal Science. “These findings provide us with a host of new targets to suppress sensory nerve activation to prevent and treat migraines and strengthen existing therapies.”

Can ketones enhance cognitive function and protect brain networks?

Friday, May 31, 2024

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester have identified mechanisms in the brain’s hippocampal network that are rescued by ketones. These findings build on previous research showing that ketones can alleviate neurological and cognitive affects.

As we age our brain naturally becomes more insulin resistant. This creates a breakdown in communication between neurons, causing symptoms like changes in mood, cognitive decline, and eventually neurodegeneration. Nathan A. Smith, M.S., PhD ('13), associate professor of Neuroscience, and fellow researchers studied the mechanisms in the brain that break down when insulin resistance is suddenly present, like in trauma, but before symptoms manifest into chronic conditions, like diabetes or Alzheimer’s.

"Once neuronal function is lost, there is no recovering the connection, so we need to identify when the function first becomes impaired," said Smith, the principal investigator of this research, published in the journal PNAS Nexus. "This study accomplishes that by bringing us closer to understanding how to rescue the function of impaired neurons and prevent or delay devastating diseases like Alzheimer's."

Majewska Lab Member Shares How Figures Help Effectively Communicate Science

Thursday, May 9, 2024

MaKenna Cealie, a neuroscience graduate student in the Majewska lab, was recently interviewed about how she uses figures and illustrations in her research. The article on BioRender highlights the importance of communicating science effectively, the figure she is most proud of, and how she has even what she enjoys doing outside of the lab.  

Using a cellular approach, Cealie aims to understand the affected mechanisms of fetal alcohol spectrum disorders (FASD). She was awarded an F31 by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to study microglia dynamics and their interactions with Purkinje cells after developmental ethanol exposure, using two-photon, in vivo imaging. 

Maiken Nedergaard receives Nakasone Award

Wednesday, May 1, 2024

Maiken Nedergaard, a professor of neurology, has been recognized by the International Human Frontier Science Program Organization with its 2024 Nakasone Award for her “groundbreaking discovery and exploration” of the glymphatic system, the brain’s unique waste removal system, and the role that sleep plays in its function.

Nedergaard is codirector of the Center for Translational Neuromedicine, which maintains research facilities at the University of Rochester Medical Center and the University of Copenhagen. In 2012, her lab first described the glymphatic system, a previously unknown network of channels that piggybacks on blood vessels. The system is used to transport cerebrospinal fluid deep into brain tissue and flush away toxic waste, including beta amyloid and tau, two proteins associated with Alzheimer’s disease.

• Learn more about the award and Nedergaard’s pioneering research.

Doug Portman named a fellow of the AAAS

Thursday, April 18, 2024

Douglas Portman, PhD, holds the Donald M. Foster, MD Professorship in Biomedical Genetics and is a professor of Neuroscience and Biology at the University of Rochester Medical Center, was named a Fellow of the American Association for the Advancement of Science (AAAS). AAAS is the world’s largest general scientific society and publisher of the journal Science.

Each year the AAAS Council elects members whose “efforts on behalf of the advancement of science, or its applications, are scientifically or socially distinguished.” Portman, a member of the University’s Del Monte Institute for Neuroscience, was elected a Fellow for his “distinguished contributions to the field of behavioral neuroscience, particularly for elucidating mechanisms of sexual dimorphism of behavior, and for outstanding mentoring of the next generation of neuroscientists.”

Michele Rucci featured in Newsweek article - "Scientists reveal hidden benefit of blinking"

Tuesday, April 16, 2024

Blinking not only keeps our eyes moist, it also plays a key role in how we process visual information, a new study has found.

“It adds to a growing body of evidence—in good part from our laboratory—showing that the visual system is very sensitive to temporal changes and uses them to represent spatial information,” says Michele Rucci, a professor of brain and cognitive sciences and at the Center for Visual Science.

New Imaging Method Illuminates Oxygen's Journey in the Brain

Thursday, March 28, 2024

The human brain consumes vast amounts of energy, which is almost exclusively generated from a form of metabolism that requires oxygen.  While the efficient and timely delivery of oxygen is known to be critical to healthy brain function, the precise mechanics of this process have largely remained hidden from scientists. 

A new bioluminescence imaging technique, described today in the journal Science, has created highly detailed, and visually striking, images of the movement of oxygen in the brains of mice.  The method, which can be easily replicated by other labs, will enable researchers to more precisely study forms of hypoxia in the brain, such as the denial of oxygen to the brain that occurs during a stroke or heart attack. The new research tool is already providing insight into why a sedentary lifestyle may increase risk for diseases like Alzheimer’s. 

“This research demonstrates that we can monitor changes in oxygen concentration continuously and in a wide area of the brain,” said Maiken Nedergaard, co-director of the Center for Translational Neuromedicine (CTN), which is based at both the University of Rochester and the University of Copenhagen. “This provides us a with a more detailed picture of what is occurring in the brain in real time, allowing us to identify previously undetected areas of temporary hypoxia, which reflect changes in blood flow that can trigger neurological deficits.” 

Nedergaard Recognized with Nakasone Award for Pioneering Research

Tuesday, March 26, 2024

Maiken Nedergaard, MD, DMSc, has been recognized by the International Human Frontier Science Program Organization (HFSPO) with its 2024 Nakasone Award for her “groundbreaking discovery and exploration” of the glymphatic system, the brain’s unique waste removal system, and the role that sleep plays in its function.  

“Dr. Nedergaard forever changed the way we understand sleep as an essential biological function that promotes brain health and plays a crucial role in preventing diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases,” said HFSPO secretary-general Pavel Kabat. “It is a fundamental discovery worthy of being honored with the 2024 HFSPO Nakasone Award.”

Nedergaard is co-director for the Center for Translational Neuromedicine, which maintains research facilities at the University of Rochester Medical Center and the University of Copenhagen.  In 2012, her lab first described the glymphatic system, a previously unknown network of channels that piggybacks on blood vessels.  The system is used to transport cerebrospinal fluid deep into brain tissue and flush away toxic waste, including beta amyloid and tau, two proteins associated with Alzheimer’s disease. 

Turns out—male roundworms are picky when choosing a mate, new research finds

Monday, March 11, 2024

A piece of rotting fruit is likely covered in hundreds if not thousands of microscopic roundworms, including C. elegans—a popular experimental model system for studying neurogenetics. With a lifespan of only a few weeks, C. elegans must reproduce quickly and often. The species is made up of hermaphrodites and males. The hermaphrodites have female bodies, can self-fertilize, and can mate with males. Recent research from of the Portman Lab at the Del Monte Institute for Neuroscience at the University of Rochester, found the males do not mate indiscriminately—they are selective about things like age, mating history, and nutrition.

“We have been aware of many of the mating cues this species uses, but this is the first time we have been able to look at them together to learn more about what they tell a male about a potential mate,” Doug Portman, PhD, professor of Biomedical Genetics said. “Assessing a mate’s characteristics seems to be something that only the male does. Understanding sex differences in C. elegans gives us important insight into how genes influence the function of neurons and circuits to guide innate behaviors—like choosing a mate.”

C. elegans is an invaluable tool to neuroscience research. Scientists have identified all of the roundworm’s neurons—there are only a few hundred of them—and the connections between its neurons have also been mapped, providing a model for understanding how neuronal circuits work in humans. It is well understood that mating is a priority for male C. elegans. Previous research out of the Portman lab found male C. elegans will suppress the ability to locate food in order to find a mate.

In a study out today in Current Biology, the Portman lab conducted experiments to observe how roundworms in petri dishes choose between potential mates. They discovered that the male worms used diverse chemical (pheromones) and physical (touch) signals to determine the sex, age, nutritional health, and mating history of the hermaphrodites. Researchers found male worms can determine a hermaphrodite’s nutritional status—whether it is healthy or food-deprived—and whether it has previously mated. When given a choice, the males showed preference toward hermaphrodites that have not previously mated with another male and are nutritionally healthy. However, once a hermaphrodite is a few days old—approaching middle age for a worm—it puts out a powerful sex pheromone that attracts males over long distances. That is because it starts to run out of its own sperm, so finding a mate becomes a more important.

Researchers find possible neuromarker for ‘juvenile-onset’ Batten disease

Monday, January 8, 2024

Early symptoms can be subtle. A child’s personality and behavior may change, and clumsiness or stumbling develops between the ages of five and ten. Over time, cognitive impairment sets in, seizures emerge or worsen, vision loss begins, and motor skills decline. This is the course of Batten disease, a progressive inherited disorder of the nervous system that results from mutations to the CLN3 gene.

“It is a devastating neurodegenerative disorder of childhood,” said John Foxe, PhD, director of the Del Monte Institute for Neuroscience and co-director of the University of Rochester Intellectual and Developmental Disabilities Research Center (UR-IDDRC), “and while it is very rare, it is important to study and understand because it could inform what we know and how we treat it and other related rare diseases.”

In a new study, out today in the Journal of Neurodevelopmental Disorders, Foxe and a team of researchers from the University of Rochester Medical Center may be closer to that goal of understanding. The paper describes how they measured changes in brain function of participants with CLN3 disease, also known as 'juvenile-onset' Batten disease. Researchers found that the functioning of the auditory sensory memory system—the brain system required for short-term memory recall—appears to decrease as the disease progresses. They revealed this by utilizing electroencephalographic recordings (EEG) to measure the brain activity of participants with and without Batten disease as they passively listened to simple auditory beeps. The participants simultaneously watched a video of their favorite movie while the brain responses to these beeps were being measured. In the participants with Batten disease, the EEG revealed a decline in the response from the auditory sensory memory system as the disease progressed. There were no significant changes among the other participants. This finding suggests that this easy-to-measure brain process may be a target or biomarker in measuring treatment outcomes in clinical trials.

“We needed to find a task that did not require explicit engagement or attention, and this is one of those kinds of tasks,” Foxe said. “The brain produces the signal that we're looking at, regardless of whether the participant is paying attention to the beeps or not. It is an objective method that provides new insight into the brain function of a population with varying communication abilities.”

Researchers identify path to prevent cognitive decline after radiation

Wednesday, January 3, 2024

Researchers at the Del Monte Institute for Neuroscience at the University of Rochester find that microglia—the brain’s immune cells—can trigger cognitive deficits after radiation exposure and may be a key target for preventing these symptoms. These findings, out today in the International Journal of Radiation Oncology Biology Biophysics, build on previous research showing that after radiation exposure microglia damage synapses, the connections between neurons that are important to cognitive behavior and memory.

“Cognitive deficits after radiation treatment are a major problem for cancer survivors," M. Kerry O’Banion, MD, PhD, professor of Neuroscience, member of the Wilmot Cancer Institute, and senior author of the study said. “This research gives us a possible target to develop therapies to prevent or mitigate against such deficits in people who need brain radiotherapy.”

Using several behavioral tests, researchers investigated the cognitive function of mice before and after radiation exposure. Female mice performed the same throughout, indicating a resistance to radiation injury. However, researchers found male mice could not remember or perform certain tasks after radiation exposure. This cognitive decline correlates with the loss of synapses and evidence of potentially damaging microglial over-reactivity following the treatment.

Researchers then targeted the pathway in microglia important to synapse removal. Mice with these mutant microglia had no cognitive decline following radiation. And others that were given the drug, Leukadherin-1, which is known to block this same pathway, during radiation treatment, also had no cognitive decline.

“This could be the first step in substantially improving a patient's quality of life and need for greater care,” said O’Banion. “Moving forward, we are particularly interested in understanding the signals that target synapses for removal and the fundamental signaling mechanisms that drive microglia to remove these synapses. We believe that both avenues of research offer additional targets for developing therapies to help individuals receiving brain radiotherapy.”

O’Banion believes this work may have broader implications because some of these mechanisms are connected to Alzheimer's and other neurodegenerative diseases.

Additional authors include first author Joshua Hinkle, PhD, postdoctoral fellow at the National Institute on Drug Abuse and former graduate student in the O’Banion-Olschowka Labs, John Olschowka, PhD, and Jacqueline Williams, PhD, of the University of Rochester Medical Center. This research was supported by the National Institutes of Health, and NASA.