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Neuroscience, Research

Exploring the role of prion-like proteins in memory disorders

Exploring the role of prion-like proteins in memory disorders

Over on the Mind the Brain blog, Stanford psychiatrist Shaili Jain, MD, discusses disorders of memory, including post-traumatic stress disorder and Alzheimer’s, with Nobel Laureate Eric Kandel, MD.

Ongoing research conducted by Kandel has helped scientists better understand the basic molecular mechanisms underlying learning and memory. His latest study showed how prion-like proteins, which are similar to the prions behind bovine spongiform encephalopathy and Creutzfeld-Jakob disease, are key for maintaining long-term memories in mice – and likely other mammals.

In Jain’s conversation with Kandel, she asks him how these new findings may translate clinically and impact patients diagnosed with memory disorders. He responds:

We are already there in some areas. We have far to go in other areas, but I will give you an example. We have a pretty good understanding of Alzheimer’s disease. We know the toxicity of beta amyloid. We do not know why the drugs that are directed against beta amyloid do not work, but one possibility that is being seriously entertained is that by the time the patient comes to see a physician, they have had the disease for ten years. That is a very long time and you lose a lot of nerve cells in ten years, and drugs do not bring nerve cells back once they are dead.

We need to diagnose the disease earlier and a major effort now, in Alzheimer’s research, is early diagnosis. Imaging, cerebral spinal fluid, genetic warning signals etc.

The other thing is it has proven possible to define an independent disorder, age related memory loss. Recent work from our lab, and that of Scott Small, has shown there is a separate entity, independent of AD, called Age Related Memory Loss. We have identified the molecular pathways involved in that disorder. We have treatments that work very effectively in animals. I think the time is going to come soon when these will be tried in people.

All of these came out from a basic science and work with experimental animals. So even though we are in the very early stage of understanding the really complex functions of the brain, we are making progress and all of this will hopefully have some therapeutic impact.

Previously: Memory of everyday events may be compromised by sleep apnea, Malfunctioning glia – brain cells that aren’t nerve cells – may contribute big time to ALS and other neurological disorders and The state of Alzheimer’s research: A conversation with Stanford neurologist Michael Greicius

Behavioral Science, Genetics, Neuroscience

Wishing for a genetic zodiac sign: How much can genes really tell us about personality?

Wishing for a genetic zodiac sign: How much can genes really tell us about personality?

Brain MRIGiven all the recent news on how gene expression influences our brain, from Alzheimer’s to addiction and even our personalities, readers might come away thinking that we’re close to breaking the code and using genetics to understand why we behave the way we do. But, things aren’t that simple.

In a post on the science blog Last Word on Nothing, Eric Vance explores what getting your personal genetic sequence means for your personality – something he calls, tongue-in-cheek, “a genetic tarot card.”

Vance delves into an explanation of one specific mutation in the COMT gene. The gene creates an enzyme that neutralizes dopamine, a neurotransmitter. The gene comes in two forms, and the difference in these two forms is just one base-pair, the individual links in our DNA code. One version of the resulting enzyme is efficient at clearing away extra dopamine. But if the gene codes for the other version, “then the enzyme becomes a wastrel… Work piles up and the brain accumulates a bunch of extra dopamine.”

Because dopamine is such a powerful regulator of mood, and by extension personality, Vance then describes, in surprising detail, personality types he expects people with either version of the gene to have. But genetic information like this is meant to be used at the population, not personal, level. In fact, none of the people in his circle of friends who have had their genome sequenced turns out to be who he expects them to be (which begs the question, how many people does he know who’ve had their DNA sequenced?). Disappointed, he laments:

But that’s not how I want it work. While I don’t like the idea of boiling human emotions down to a couple squishy turning gears, I do like how tidy it is. I want to be able to look up my genome and make broad generalizations about myself. I want to have a genetic tarot card that I can inspect and say “ohhh, that’s why I always forget people’s names” or “that’s why I got in that fight in the third grade.”

Vance concludes, “But that’s not what nature gave us. Nature has given us messy, confusing and vastly complicated brains.” We are more, it turns out, than the sum of our base pairs.

Previously: New research sheds light on connection between dopamine and depression symptoms

Photo by deradrian

Aging, Ask Stanford Med, Chronic Disease, Neuroscience, Women's Health

Exploring Alzheimer’s toll on women

Exploring Alzheimer’s toll on women

Julianne Moore AlzheimersIn last year’s “Still Alice,” Julianne Moore’s portrays a woman beset by early-onset Alzheimer’s Disease. It’s fitting that the academy-award winning film (Moore garnered a Best Actress award for her role) about Alzheimer’s features a woman as the central character because the illness disproportionately affects women.

The BeWell@Stanford blog recently featured a Q&A with Stanford neurologist and Alzheimer’s researcher Michael Greicius, MD, MPH about Alzheimer’s and women. The piece covers the effects of the disease, but I was intrigued to read about the challenges for caregivers of people with the disease (who are also disproportionately women):

Most of the caregivers of people with Alzheimer’s Disease are women. Do you have any advice for them in terms of how they can take care of themselves while taking care of a loved one with the disease?

This gets to the damned-if-you-do, damned-if-you-don’t aspect of AD and women. On the one hand, women are more likely to develop AD; on the other hand, they are also more likely to find themselves as the primary caregiver for someone with AD. It is now well known that caring for someone with AD has a powerful, negative impact on physical and emotional well-being. Particularly as the disease progresses and patients require more care, there is a large physical toll taken when, for example, having to lift patients out of a chair or off the toilet or out of bed. Sleep becomes fractured for the patient. which means it becomes fractured for the caregiver.

Some of the questions also dealt with the fact that despite the recent advances in Alzheimer’s research, we still don’t completely understand how the disease works or how it can be prevented:

What can we do to reduce our risk for developing the disease?

We do not know of anything that definitely reduces a person’s risk of developing Alzheimer’s, although there is strong data to suggest that regular aerobic exercise and a heart-smart diet will reduce risk. Head trauma is an important risk factor for AD and another type of dementia, so minimizing exposure to head trauma can also reduce risk of AD. Numerous companies make explicit or implicit claims about their “nutraceutical” or vitamin or “brain-training” software being able to stave off AD. None of these claims are true and most, if not all, of these purveyors are modern-day snake-oil salesmen and saleswomen.

But Greicius is optimistic and pointed out that Stanford recently became an NIH-sponsored Alzheimer’s Disease Research Center, which means we can build upon Stanford’s past “ground-breaking Alzheimer’s research.”

Previously: Are iron, and the scavenger cells that eat it, critical links to Alzheimer’s?Alzheimer’s forum with Rep. Jackie Speier spurs conversation, activismScience Friday explores women’s heightened risk for Alzheimer’s and The toll of Alzheimer’s on caretakers
Photo by Maria Morri

Humor, Media, Medicine and Society, Neuroscience, Research, Stanford News

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?

Did extraterrestrials chew up my news release, or does artificial intelligence still have a ways to go?


Almost two years ago, in a Scope blog entry titled “Can Joe Six-Pack compete with Sid Cyborg?” I posed the question: “Just how long will it be before we can no longer tell our computers from ourselves?”

I think it’s safe to say we’re not there yet. Either that, or extraterrestrials have been reading my news releases and finding them puzzling.

Last week we put out a news release I’d written about a dramatic discovery by Stanford radiologists Mike Zeineh, MD, PhD, Brian Rutt, PhD, and their colleagues. In brief, they’d analyzed postmortem slabs of brain tissue from people diagnosed with Alzheimer’s, compared them with equivalent brain-tissue slabs taken from people who’d died without any Alzheimer’s-like symptoms, and noticed some striking and intriguing differences. In a key brain region essential to memory formation, Zeineh and Rutt had spotted – only in Alzheimer’s brains, not normal ones – iron deposits engulfed by mobile inflammatory cells. This observation’s potentially big implications were plenty newsworthy.

It so happened that, on the day we issued the release, a high-powered five-day-long meeting on Alzheimer’s sponsored by the eponymous Alzheimer’s Association was in session in Washington, D.C. As a result, many of the brain-oriented science writers to whom my news release was targeted were preoccupied.

I was a little anxious about that. So, the other day, I turned to my favorite search engine to see if the release had managed to get some traction in the popular press. As I’d feared, the Washington conference had sucked up a lot of the oxygen in the earthly neuroscience arena.

But apparently, the release had done better in Outer Space. I saw that it had been picked up by, for example, Red Orbit (a website that I’ve always assumed, based on its name, emanates from Mars).

My eyes were next drawn to a link to an unfamiliar outfit called AZ News, which bills itself in a tagline as an “International Online News Site.” I clicked on the link, and saw a news report with the same title as my release. I started reading the text below.

The first words were: “In autopsy mind hankie from people not diagnosed with Alzheimer’s…” I don’t know what an “autopsy mind hankie” is, but I suspect it’s a mind-blower.

I checked our release. That’s not what I’d written at all. What I’d said was, “In postmortem brain tissue from people not diagnosed with Alzheimer’s…”

It seemed pretty clear that the release had been translated into some language – I had no idea which – and then, for some reason, reverse-translated back into English. I read on.

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Autism, Behavioral Science, Neuroscience, Pediatrics, Research, Stanford News

A new insight into the brain chemistry of autism

A new insight into the brain chemistry of autism

TrueHugFor several years now, scientists have been testing the hypothesis that one particular hormone, oxytocin, plays a role in autism. It seems logical: After all, this molecule nicknamed the “love hormone” promotes bonding between romantic partners and is one of the main signals involved in childbirth, breastfeeding and helping new mothers form strong bonds with their babies. And social-interaction difficulties are a known characteristic of autism, a developmental disorder that affects one in every 68 kids.

But in the flurry of interest around oxytocin, a related signaling molecule has been largely overlooked. Called vasopressin, it’s structurally very similar to oxytocin. Both are small proteins made of nine amino acids each, and the amino-acid sequence is identical at seven of the nine spots in the two hormones. Vasopressin is best known for its role in regulating blood pressure, but it also has social roles, which have mostly been studied in rodents.

Noting the dearth of autism-vasopressin research, a Stanford team decided to study vasopressin levels and social behavior in children diagnosed with autism and controls who had not been diagnosed with autism. Our press release about their study, which was published today in PLOS ONE, explains:

The research team found a correlation between low levels of vasopressin, a hormone involved in social behavior, and the inability of autistic children to understand that other people’s thoughts and motivations can differ from their own. …

“Autistic children who had the lowest vasopressin levels in their blood also had the greatest social impairment,” said the study’s senior author, Karen Parker, PhD, associate professor of psychiatry and behavioral sciences.

Parker and her colleagues examined “theory of mind,” the ability to deduce that others have a mind of their own – and that they may perceive the world differently than you do. It’s an important underpinning to forming empathetic relationships with other people. In kids with autism, the lower their vasopressin levels, the worse their scores on a test of theory of mind, the study found. Children without autism did not show this link; they all had pretty good theory of mind scores, whether their vasopressin levels were low or high.

It’s worth adding that low vasopressin level did not diagnose whether a child had autism; the hormone’s levels ranged from low to high in both groups of children. So autism is not simply a state of vasopressin deficiency. However, the researchers are interested in whether giving vasopressin might help relieve autism symptoms and are now carrying out a clinical trial to test its effects.

The work also provides an interesting complement to oxytocin findings published by the same team last year. In the oxytocin study, the scientists found that children with autism could have low, medium or high oxytocin levels, just like other children. However, oxytocin levels were linked to social ability in all children, not just those with autism.

Based on the new findings, it’s possible, Parker told me, that vasopressin is uniquely important for children with autism. She’s eager to expand her work in this overlooked corner of brain-chemistry research.

Previously: Stanford research clarifies biology of oxytocin in autism, “Love hormone” may mediate wider range of relationships than previously thought and Volunteers sought for autism drug study
Artwork by Dimka

Imaging, Immunology, Mental Health, Neuroscience, Research, Stanford News

Are iron, and the scavenger cells that eat it, critical links to Alzheimer’s?

Are iron, and the scavenger cells that eat it, critical links to Alzheimer's?

iron linkIf you’ve been riding the Alzheimer’s-research roller-coaster, brace yourself for a new twist on that wrenching disease of old age.

In a study published in Neurobiology of Aging, Stanford radiologists Mike Zeineh, MD, PhD,  and Brian Rutt, PhD, and their colleagues used a ultra-powerful magnetic-resonance-imaging (MRI) system to closely scrutinize postmortem tissue from the brains of people with and without Alzheimer’s disease. In four out of five of the Alzheimer’s brains they looked at, but in none of the five non-Alzheimer’s brains, they found what appear to be iron-containing microglia – specialized scavenger cells in the brain that can sometimes become inflammatory – in a particular part of the hippocampus, a key brain structure that’s absolutely crucial to memory formation as well as spatial orientation and navigation.

Zeineh and Rutt told me they don’t know how the iron gets into brain tissue, or why it accumulates where it does. But iron, which in certain chemical forms can be highly reactive and inflammation-inducing, is ubiquitous throughout the body. Every red blood cell that courses through our microvasculature is filled with it. So one possibility – not yet demonstrated – is that iron deposits in the hippocampus could result from micro-injury to small cerebral blood vessels there.

As surprising as the iron-laden, inflamed microglia Zeineh, Rutt and their associates saw in Alzheimer’s but not normal brains was what they didn’t see. Surprisingly, in the brain region of interest there was no consistent overlap of either iron or microglia with the notorious amyloid plaques that have been long held by many neuroscientists and pharmaceutical companies to be the main cause of the disorder. These plaques are extracellular aggregations of a small protein called beta-amyloid that are prominent in Alheimer’s patients’ brains, as well as in mouse models of the disease.

Because they weren’t able to visualize small, soluble beta-amyloid clusters (now believed to to be the truly toxic form of the protein), Rutt and Zeineh don’t rule out a major role for beta-amyloid in the early developmental stages of pathology in Alzheimer’s.

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Neuroscience, Research, Science, Stanford News

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

Nobelist neuroscientist Tom Südhof still spiraling in on the secrets of the synapse

spiral staircase“History,” said Winston Churchill (or was it Arnold Toynbee or Edna St. Vincent Millay?), “is just one damn thing after another.” In many respects, so is good science.

And that’s just how it should be, Stanford neuroscientist and molecular physiologist Tom Südhof, MD, told me a few years ago when I interviewed him for a story I wrote in connection with the Lasker Award, a prestigious prize he’d won shortly before receiving the 2013 Nobel Prize in physiology or medicine:

Asked to recall any defining “eureka!” moments that had catapulted his hunches forward to the status of certainty, Südhof noted that in his experience, science advances step by step, not in jumps. “I believe strongly that most work is incremental,” he said. The systematic solution of highly complex problems requires a long view and plenty of patience.

Climbing a long ladder to the Nobel one small step at a time, Südhof continually raised the power of his conceptual microscope over the decades as he probed the intricate workings of synapses: the all-important junctions in the nervous system where information, in the form of chemical messengers called neurotransmitters, gets passed from one nerve cell to another.

From an explanation of Südhof’s synaptic studies:

The firing patterns of our synapses underwrite our consciousness, emotions and behavior. The simple act of taking a step forward, experiencing a fleeting twinge of regret, recalling an incident from the morning commute or tasting a doughnut requires millions of simultaneous and precise synaptic firing events throughout the brain and peripheral nervous system.

A philosopher might say that synapses collectively constitute the physiological substrate for the soul. A futurist might write (as I once did):

With nanobots monitoring every critical neural connection’s involvement in a thought or emotion or experience, you’ll be able to back up your brain – or even try on someone else’s – by plugging into a virtual-reality jack. The brain bots feed your synapses the appropriate electrical signals and you’re off and running, without necessarily moving.

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Neuroscience, Stanford News, Videos

Are decisions driven by subconscious desires or shaped by conscious goals?

Are decisions driven by subconscious desires or shaped by conscious goals?

Throughout our lives, we often encounter perplexing situations involving other individuals or read in the news about someone’s seemingly irrational decision and say to ourselves: What were they thinking? In this Stanford+Connects video, Bill Newsome, PhD, director of the Stanford Neurosciences Institute, and his wife Brie Linkenhoker, PhD, a neuroscientists-turned-strategist who directs Worldview Stanford, examine the process of decision making and the role of impulses and self-control. Watch the full talk to learn more about the mechanisms driving us to make decisions.

Previously: Exploring the science of decision making and Exploring the intelligence-gathering and decision-making processes of infants

Mental Health, Neuroscience

No time for a vacation? Take a break without leaving the office

No time for a vacation? Take a break without leaving the office

3863917188_4972c8fe11_zWhen you’re tired, overworked and stressed out, a good vacation can be just what the doctor ordered. The catch is that it’s not always easy to take a break when you need it most. If you’re nodding your head in agreement, check out this Harvard Business Review piece by Emma Seppälä, PhD, associate director of Stanford’s Center for Compassion and Altruism Research and Education.

As Seppälä explains in her piece, workers in the United States tend to have less vacation days than employees elsewhere. Moreover, many people find it hard to truly “unplug” when they finally do take a vacation because smartphones, Wi-Fi and other electronic devices are so readily available.

But, fewer vacation days and smartphones aren’t entirely to blame for the bloated work schedules that are ubiquitous here and elsewhere. As Seppälä explains, many salaried employees with ample vacation time sometimes feel they can’t take an extended holiday because vacations are not “productive” and being out of the office, and out of touch, can have negative repercussions.

“Unfortunately, the logic of both employees and employers is highly flawed,” Seppälä writes. “Both fail to realize that cutting into vacation time is actually detrimental to both organizations and their employees both in terms of financial and productivity costs.” One short-term solution that can help employees endure a long period of work is a “mini-break”— a vacation that’s compressed into a few hours and can be taken virtually anywhere. She elaborates:

Research by Sabine Sonnentag suggests that detaching from work is essential to enhanced productivity. Her work has shown that, while people who do not detach from work suffering from greater levels of exhaustion, those who do recover from job stress and are more likely to have higher engagement levels at work.

If you really can’t take a proper vacation, Adam Rifkin, successful Silicon Valley serial entrepreneur and founder of PandaWhale, suggests “taking a little downtime every day rather than pushing it off for some getaway week.” Sonnentag’s research also suggests that if you make an effort to completely disengage from work when the workday is over – by, for example, engaging in a hobby you enjoy, exercising, or taking a walk in nature – you will reap the benefits: you will feel less fatigued, more engaged at work, and more energized when you leave work.

Stopping to smell the roses can make a big difference in your overall well-being during periods of high work flow, but a mini-break is no substitute for the real thing. So, if you absolutely can’t take an extended vacation, make the most of the downtime you have. Just be sure you also find a way to take that long vacation you’ve been dreaming of.

Previously: Exposure to nature helps quash depression – so enjoy the great outdoors!Seven ways laughter can improve your well-beingWhat email does to your brain and How social connection can improve physical and mental health and Out-of-office autoreply: Reaping the benefits of nature
Photo by Joe Penniston

In the News, Neuroscience, Research

A year-long trip: One patient’s drug use linked to Alice in Wonderland syndrome

A year-long trip: One patient's drug use linked to Alice in Wonderland syndrome

8303093547_968a17bc4f_zA mind-bending condition long known for its associations with migraines may have another cause: acid use. Sufferers of Alice in Wonderland syndrome, a neurological disorder named in 1955, experience distortions of proportions: The world does not appear as it should be. Instead, it is too small, too close, too big or too far, just as was the case for the main character of the classic novel after eating a very small cake that read “EAT ME:”

“Good-bye feet!” said Alice, for when she looked down at her feet, they seemed to be almost out of sight, they were getting so far off. “Oh my poor little feet, I wonder who will put on your shoes and stockings for you now, dears? I’m sure I shan’t be able.”

For decades, this rare syndrome has been linked to migraines, but a new case report in the Israel Journal of Psychiatry shows that for one patient, it was brought on by LSD use — with his symptoms continuing for a year after the drug use has stopped.

Although researchers aren’t sure what caused the patient to experience the ongoing symptoms, the syndrome is generally caused by a hypersensitivity of the brain. Stanford neurologist Sheena Aurora, MD, explains in a LiveScience article:

This hypersensitivity typically starts in the occipital lobe, the visual region at the back of the brain. However, it can spread to the parietal lobes… which discern sizes and shapes, Aurora said.

Scholars have speculated that Lewis Carroll experienced migraines, which might have inspired Alice’s atypical adventures.

Previously: Director of Stanford Headache Clinic answers your questions on migraines and headache disorders, Advice on managing migraines and More attention, funding needed for headache care
Image by new 1luminati

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