Published by
Stanford Medicine

Category

Neuroscience

Genetics, Neuroscience, Research, Science, Stanford News

Yeast advance understanding of Parkinson’s disease, says Stanford study

Yeast advance understanding of Parkinson's disease, says Stanford study

It’s amazing to me that the tiny, one-celled yeast can be such a powerful research tool. Now geneticist Aaron Gitler, PhD, has shown that the diminutive organism can even help advance the understanding of Parkinson’s disease and aid in identifying new genes involved in the disorder and new pathways and potential drug targets. He published his findings today in Neuron and told me in an email:

Parkinson’s disease is associated with many genetic and environmental susceptibility factors. Two of the newest Parkinson’s disease genes, EIF4G1 and VPS35, encode proteins involved in protein translation (the act of making protein from RNA messages) and protein sorting (shuttling proteins to the correct locations inside the cell), respectively. We used unbiased yeast genetic screens to unexpectedly discover a strong genetic interaction between these two genes, suggesting that the proteins they encode work together.

The proteins, EIF4G1 and VPS35, have changed very little from yeast to humans. Gitler and his colleagues showed that VPS35 interacts functionally with another protein implicated in Parkinson’s disease, alpha-synuclein, in yeast, round worms and even laboratory mice. As Gitler described:

Together, our findings connect three seemingly distinct Parkinson’s disease genes and provide a path forward for understanding how these genes might contribute to the disease and for identifying therapeutic interventions. More generally, our approach underscores the power of simple model systems for interrogating even complex human diseases.

Previously: Researchers pinpoint genetic suspects in ALS and In Stanford/Gladstone study, yeast genetics further ALS research

Clinical Trials, Emergency Medicine, Neuroscience, Research

Clinical trial shows progesterone doesn’t improve recovery from head trauma

Clinical trial shows progesterone doesn't improve recovery from head trauma

800px-thumbnailResearchers had high hopes that progesterone, that multipurpose endogenous steroid, could stave off some of the worst effects of head injuries. A quick injection soon after a blunt trauma and  — wa-zam — marked improvement on the widely used Glasgow Outcome Scale, which measures brain injuries on a scale from death to low disability. Or so they thought.

Instead, a nationwide clinical trial was called off after early analyses showed no benefit. The findings were published last week in The New England Journal of Medicine.

“These results are plainly disappointing,” said lead investigator David Wright, MD, an emergency medicine physician at Emory University, in an Emory release.

Stanford, in partnership with Santa Clara Valley Medical Center and the Regional Medical Center of San Jose, enrolled approximately 80 patients in the study between 2008 and 2013, said James Quinn, MD, a Stanford emergency medicine physician. Quinn said there were many benefits to the study even though the results didn’t suggest an improvement.

“The patients all got great care,” Quinn said.  The care teams worked to ensure the care was standardized and top notch for study participants, he said. In addition, there’s still a possibility that progesterone administered closer to the time of injury might help patients. To adhere with study protocols, the teams had to wait one hour after the patient arrived at the emergency room before providing the progesterone or placebo, Quinn said.

The study had a unique design, in part because emergency trauma patients can often not provide consent. Instead, the research team publicized the study before starting and gave participants the opportunity to opt out when they were able.

Quinn also made note of an observation made by he and his colleagues:  Although nationwide most injuries stemmed from vehicle crashes, the Stanford-led teams saw an abundance of bicycle accidents.

Previously: For prolonged seizures, a quick shot often does the trick, study finds, Stanford Medicine story on surviving brain injury wins health journalism award and Estradiol — but not Premarin — prevents neurodegeneration in women at heightened dementia risk
Photo by U.S. Navy

Chronic Disease, Neuroscience, Parenting, Pediatrics, Research

High blood sugar linked to reduced brain growth in children with Type 1 diabetes

High blood sugar linked to reduced brain growth in children with Type 1 diabetes

Some areas of the brain grow more slowly in children with Type 1 diabetes than those without, according to findings published this week in Diabetes. Researchers also found that children with the highest and most variable blood sugar levels had the slowest brain growth.

Glucose, the main form of sugar in our blood, is the brain’s primary fuel, and in Type 1 diabetes, the body loses the ability to produce a key hormone needed to regulate blood sugar levels. Type 1 diabetes treatment for children has often focused on making sure their glucose levels don’t get too low, since very low glucose can quickly put someone into a coma. But it’s emerging that chronically-high sugar is also bad for the brain.

The better the glucose control, the more likely that a child’s brain development will be unimpeded.

The new study, conducted at Stanford and four other universities, tracked brain structure and cognitive function in 144 young children with Type 1 diabetes and a comparison group of 72 children without diabetes over 18 months. MRI scans showed that the brains of both groups of kids were growing, but gray- and white-matter growth was slower in several areas of the brain in the diabetic children.

“These studies provide strong evidence that the developing brain is a vulnerable target for diabetes complications,” the researchers wrote. The affected brain areas have a variety of roles, including visual-spatial processing; auditory, language and object processing; executive function; spatial and working memory; and integration of information from sensory systems.

I asked two of the paper’s Stanford authors for more thoughts about what they found.

“The magnitude of the group differences in brain growth over time was surprising,” said Allan Reiss, MD, the study’s senior author. “I actually thought these differences would be more subtle — they were not.”

Past studies have found cognitive and brain-structure changes associated with diabetes in older patients, but this research stands out because the kids included were so young — at the start of the study, their ages ranged from 4 to just under 10, with an average age of 7 — and because the study had a prospective design, following children forward in time. In addition to examining brain structure, the researchers also tested the kids’ cognitive function with standard tests of IQ, learning and memory, and mood and behavior, among others. They saw no significant differences in cognitive function between the two groups, a finding Reiss said did not surprise him.

Continue Reading »

Behavioral Science, Global Health, Neuroscience, Stanford News

Stanford Rhodes Scholar heading to Oxford to study ways "the brain can go awry"

Stanford Rhodes Scholar heading to Oxford to study ways "the brain can go awry"

10515175_10152524157302002_5878205180193467577_o-001Undergraduate Emily Witt is one of two Stanford students selected to receive the prestigious Rhodes Scholarship to study abroad at Oxford next year; an announcement was made late last month.

Witt is a human biology major with a concentration in neuropathology, and she’s minoring in psychology. Her research experience thus far spans neuroscience, psychology, autoimmune pathology, and health in the developing world; and she says she’s interested in studying “any way that the brain or the nervous system can go awry.”

Witt, who plans to attend medical school after her scholarship tenure, works in the lab of  neurologist Lawrence Steinman, MD, PhD, which seeks to understand the pathogenesis of autoimmune diseases, particularly multiple sclerosis. She’s using the lab to conduct research for her honors thesis, which focuses on the mechanisms of vitamin D in multiple sclerosis. She’s also involved with the Center for Interdisciplinary Brain Sciences Research and has participated in various studies related to autism and social cognition.

After hearing about this honor, I reached out to Witt with some questions about her work and her future plans:

How did you become interested in this field?

I’m interested in MS for two reasons. On a personal level, I have seen the devastating impact of the disease first-hand as my uncle has the progressive form of MS. Watching his condition worsen, and seeing the impact it has had on his life and the life of my aunt and cousins, inspired me to research this horrible disorder.

On an intellectual level, I’m fascinated by the interaction between the immune system and the brain. I believe it’s an incredibly important area of research as the immune system is a contributing factor to numerous neurological diseases, from multiple sclerosis and autism to depression.

What makes Oxford a particularly appealing place for you to study? Who or what do you hope to work with there?

I’m interested in working with two neuroscientists who are experimental psychologists; they’re actually bridging the gap between experimental psychology and neuroscience, which are the two degrees I’m hoping to pursue while at Oxford. One is Elaine Fox, who researches cognitive biases, and the other is Catherine Harmer, [who studies the] pharmacological aspects of depression and how they affect cognitive biases, particularly with respect to depression and anxiety.

Are you interested in contextual understandings of disease or degeneration – its social roots? How does interdisciplinary work fit into your imagining of what you’re doing and would like to do?

That’s what my primary motivation going forward is: kind of connecting what I see in everyday life and how neurological [diseases] manifest and what I understand about them biologically. So what I’m really interested in is combining a fundamental understanding of psychology with clinical applications of neuroscience… Because I do think that… there’s still a wide gap between studying the brain on a molecular and cellular level, and studying it on a behavioral level.

Continue Reading »

Immunology, Neuroscience, Research, Stanford News

Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice

Blocking a receptor on brain’s immune cells counters Alzheimer’s in mice

brain in motionAttention, nerve cells: It’s not all about you.

As a new study in the Journal of Clinical Investigation led by Stanford neuroscientist Kati Andreasson, MD, shows, blocking the action of a single molecule situated on the surfaces of entirely different brain cells reversed memory loss and a bunch of other Alzheimer’s-like features in experimental mice.

The very term “neuroscience” strongly suggests that nerve cells, a.k.a. neurons, are the Big Enchilada in brain research – and, let’s face it, you wouldn’t want to leave home without them. But they’re far from the entire picture. In fact, neurons account for a mere 10 percent of all the cells in the brain. It may be that the mass die-off of nerve cells in the brains of people with Alzheimer’s disease may largely occur because, during the course of aging, another set of key players ensconced in that mysterious organ inside our skull and  known collectively as microglia begin to fall down on the job.

In  a release I wrote to explain the study’s findings in lay terms, I described microglia as the brain’s very own, dedicated immune cells:

A microglial cell serves as a front-line sentry, monitoring its surroundings for suspicious activities and materials by probing its local environment. If it spots trouble, it releases substances that recruit other microglia to the scene … Microglia are tough cops, protecting the brain against invading bacteria and viruses by gobbling them up. They are adept at calming things down, too, clamping down on inflammation if it gets out of hand. They also work as garbage collectors, chewing up dead cells and molecular debris strewn among living cells – including clusters of a protein called A-beta, notorious for aggregating into gummy deposits called Alzheimer’s plaques, the disease’s hallmark anatomical feature. … A-beta, produced throughout the body, is as natural as it is ubiquitous. But when it clumps into soluble clusters consisting of a few molecules, it’s highly toxic to nerve cells. These clusters are believed to play a substantial role in causing Alzheimer’s.

“The microglia are supposed to be, from the get-go, constantly clearing A-beta, as well as keeping a lid on inflammation,” Andreasson told me. If their job performance heads downhill – as seems to occur during the aging process – things get out of control. A-beta builds up in the brain, inducing toxic inflammation.

But by blocking the activity of a single molecule – a receptor protein on microglial cells’ surfaces  – Andreasson’s team got those microglia back on the job. They resumed chewing up A-beta, quashing runaway neuro-inflammation, squirting out neuron-nurturing chemicals. Bottom line: the Alzheimer’s-prone experimental animals’ IQs (as measured by mousey memory tests) rose dramatically.

Aspirin and similar drugs also tend to shut down the activity of this microglial receptor, which may or may not explain why their use seems to stave off the onset of Alzheimer’s in people who start using them regularly (typically for unrelated reasons) before this memory-stealing syndrome’s symptoms show up. But aspirin et al. do lots of other things, too – some good, some bad. The new findings suggest a compound carefully tailored to block this receptor and do nothing else might be a weapon in the anti-Alzheimer’s arsenal.

Previously: Another big step toward building a better aspirin tablet, Untangling the inflammation/Alzheimer’s connection and Study could lead to new class of stroke drugs
Photo by Henry Markham

Aging, In the News, Neuroscience, Research, Science, Stanford News

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine’s Breakthrough of the Year

Stanford research showing young blood recharges the brains of old mice among finalists for Science Magazine's Breakthrough of the Year

ballot box

Stanford research showing that an infusion of young blood recharges the brains of old mice is one of the finalists for Science magazine’s annual contest for People’s Choice for Breakthrough of the Year. Today is the last day to cast your vote. Click here if you’d like to support the work, which could lead to new therapeutic approaches for treating dementia.

Several months ago, I had the pleasure of helping break the news about this great piece of research. So, let’s face it, I take a certain amount of pride in the amount of news coverage it received and the attention it’s getting now.

But the real credit goes to Stanford neuroscientist Tony Wyss-Coray, PhD, along with his able lead author Saul Villeda, PhD, and colleagues. This important discovery by Wyss-Coray’s team revealed that infusing young mice’s blood plasma into the bloodstream of old mice makes those old mice jump up and do the Macarena – and perform a whole lot better on mousey IQ tests.

Infusing blood plasma is hardly a new technique. As Wyss-Coray told me when I interviewed him for my release:

“This could have been done 20 years ago….You don’t need to know anything about how the brain works. You just give an old mouse young blood and see if the animal is smarter than before. It’s just that nobody did it.”

And after all, isn’t that what breakthroughs are all about? It’s still too early to say, but this simple treatment – or (more likely) drugs based on a better understanding of what factors in blood are responsible for reversing neurological decline –  could someday turn out to have applications for Alzheimer’s disease and much more.

At last count, the Wyss-Coray’s research is neck-and-neck with a competing project for first place. If you think, as I do, that a discovery with this much potential deserves a vote of confidence make sure to take a moment this afternoon to cast your virtual ballot.

Previously: The rechargeable brain: Blood plasma from young mice improves old mice’s memory and learning, Old blood makes young brains act older, and vice versa and Can we reset the aging clock, once cell at a time?
Photo by FutUndBeidl

Medicine and Society, Neuroscience, Public Safety, Research, Stanford News

Smooth, safe landings stem from senior pilots, study shows

Smooth, safe landings stem from senior pilots, study shows

passenger-plane-19469_640Sometimes planes thump onto the runway. The wheels smack into the ground — bam! Other times planes bounce down — ka-thump, ka-thump, ka-thump. And once in awhile, in those most beautiful of landings, planes simply float down, the wheels gently stroke the runway, the transition from air to ground seamless and smooth.

Those landings are more likely to occur when an experienced pilot is at the helm. The experience allows top pilots to accurately assess their surroundings, while displaying less brain activity than less experienced pilots, according to a study published recently in PLOS One.

A team led by Stanford and VA Palo Alto Health Care System researchers used an fMRI machine to examine the mental activity of 20 pilots as they landed planes using a flight simulator. A Stanford release explains the study:

The trial started the pilots at 350 feet of altitude. They were instructed to begin their descent based only on their instrument readings, as would be typical in most real-life flights. Once they reached 200 feet — the altitude at which the Federal Aviation Administration mandates you must be able to clearly see the runway in order to land — the program would display the runway, either clearly or obscured by varying degrees of fog.

The pilots would then need to flash their gaze from the instruments to the runway and back to make a snap decision about whether or not it would be safe to continue the approach.

Landings are the most dangerous part of a flight.  The study showed that the more experienced pilots made correct landing decisions 80 percent of the time, while displaying only half as much brain activity. The newer pilots made correct landing decisions 64 percent of the time:

“The data show that the expert pilot seems to just know what to look for, where to look and when to look,” said Stanford psychiatrist Maheen Adamson, PhD… “And we’ve been able to trace that skill back to the caudate nucleus.”

This is an area of the brain involved in regulating gaze as the eyes quickly shift their focus to different fixed objects. The work needs to be replicated to confirm the caudate nucleus’s role in instrument scanning, Adamson added.

Adamson noted that pilot training programs may be able to improve performance using brain imaging techniques in the future.

Previously: Medical mystery solved: Stanford clinicians identify source of Navy pilot’s puzzling symptoms, Being bilingual “provides the brain built-in exercise” and Image of the Week: Uncovering brain-imaging inaccuracies
Photo by PublicDomainPictures

Imaging, Neuroscience, Patient Care, Pediatrics, Research

Stanford-led study suggests changes to brain scanning guidelines for preemies

Stanford-led study suggests changes to brain scanning guidelines for preemies

preemieOne big challenge of having a premature baby: the uncertainty. With good medical care, a great many preemies do very well, but some face long-term disabilities, medical complications and developmental delays, and others, sadly, die in infancy. Unfortunately, doctors can’t always tell how a baby will fare in the long term.

A new study, led by a Stanford team and conducted at 16 sites around the country, is part of the ongoing effort to change that. The researchers examined what type and timing of brain scans give doctors the greatest ability to predict preemies’ neurodevelopmental outcomes in toddlerhood. The research, published online today in Pediatrics, found that for babies born more than 12 weeks early who survive to near their original due dates, brain scans performed near their due date are better predictors than scans done near birth.

Most preemies already get at least one brain scan. That’s because national guidelines recommend that preemies’ doctors perform a cranial ultrasound seven to 14 days after birth to look for immediate problems such as bleeding into the brain. (Ultrasound is a good fit for the needs of fragile infants: Babies’ fontanelles provide “acoustic windows” to the brain, and ultrasound is non-invasive, uses no radiation, requires no sedation, and can be performed with a portable scanner brought to the bedside.) Some prior research has shown that these early scans can also give information about an infant’s risk of cognitive, motor and behavioral deficits or delays in childhood, but the predictive value of these early scans can be fairly low.

The new study examined both cranial ultrasound and MRI performed close to the baby’s due date, which is also when most preemies are ready to go home from the hospital. A lot changes in the brain during those first few weeks, perhaps explaining why later scans did a significantly better job of predicting which children would have persistent neurodevelopmental problems when the doctors checked in with them at 18 to 22 months of age.

“Neuroimaging may help us understand what a child’s outcome may look like, and ultimately help us focus our attention in terms of the type of follow-up and specific interventions that could best support a child after discharge from the hospital,” said Susan Hintz, MD, the study’s lead author and a neonatologist at Lucile Packard Children’s Hospital Stanford.

Continue Reading »

Aging, Neuroscience, Stanford News, Stroke, Videos

Examining the potential of creating new synapses in old or damaged brains

Examining the potential of creating new synapses in old or damaged brains

Synapses are the structures in the brain where neurons connect and communicate with each other. Between early childhood and the beginning of puberty, many of these connections are eliminated through a process called “synaptic pruning.” Stroke, Alzheimer’s disease, and traumatic brain injury can also cause the loss of synapses. But what if new synapses could be created to repair aging or damaged brains?

Stanford neurobiologist Carla Shatz, PhD, addresses this question in the above Seattle+Connect video. In the lecture, she discusses the possibility of engaging the molecular and cellular mechanisms that regulate critical developmental periods to regrow synapses in old brains. Watch the video to learn how advances at the neural level around a novel receptor, called PirB, have implications for improving brain plasticity, learning, memory and neurological disorders.

Previously: Drug helps old brains learn new tricks, and heal, Cellular padding could help stem cells repair injuries and Science is like an ongoing mystery novel, says Stanford neurobiologist Carla Shatz and “Pruning synapses” and other strides in Alzheimer’s research

Imaging, In the News, Neuroscience, Research, Stanford News

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

Studies on ME/chronic fatigue syndrome continue to grab headlines, spur conversation

neural-pathways-221719_640The proof’s in the pudding, the old saying — which seems slightly seasonal — goes. So when a Stanford team compared images of brains affected by chronic fatigue syndrome, with those healthy brains, they found noticeable differences, including misshaped white matter, the cells that coordinate communication between brain regions. The news garnered immediate attention and has now been featured in a New York Times  piece:

The relationship between the symptoms experienced by patients and the findings is unclear. The two parts of the brain connected by the abnormally shaped white matter are believed to be important for language use, said Michael Zeineh, MD, a radiologist at Stanford and the lead author…

“This opens the door to more detailed investigations because now we have targets for future research,” he said.

The Times also refers to another study, published in March, that found cerebral inflammation in patients who suffer from chronic fatigue syndrome, or, as it is also called, myalgic encephalomyelitis/ C.F.S. This is big news for a condition that’s often misdiagnosed — patients are sometimes forced to visit numerous doctors and battle insurance companies — all while fighting the debilitating symptoms — before securing a diagnosis.

The Times touches on the tricky politics of the disease as well:

Next month, a panel convened by the National Institutes of Health will hold a two-day workshop  charged with “advancing the research” on the illness of the disorder. The Institute of Medicine is conducting a separate, government-sponsored initiative to assess and evaluate the many sets of diagnostic criteria for M.E./C.F.S., with the results expected next year.

Advocacy groups have questioned the rationale for two separate efforts. They have also criticized the initiatives because in both cases many people with little or no expertise in M.E./C.F.S. will be voting on recommendations that could have a significant impact on the government’s future efforts.

Previously: Patients’ reaction to ME/CFS coverage in Stanford Medicine magazine, Some headway on chronic fatigue syndrome: Brain abnormalities pinpointed and Unbroken: A chronic fatigue syndrome patient’s long road to recovery
Image by geralt

Stanford Medicine Resources: