Friday, June 24, 2022

Study Links Depression with High Levels of an Amino Acid

 reposted from


Study Links Depression with High Levels of an Amino Acid

Experiments in animals and observations in humans suggest that the amount of proline circulating in one’s plasma has a strong association with depression severity.

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Dan Robitzski
Jun 14, 2022
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ABOVE:Bacteria in the gut© ISTOCK.COM, ARTUR PLAWGO

A growing body of literature ties the gut microbiome to symptoms of depression in a seemingly circular relationship where each affects the other. However, many of the studies on this relationship merely link certain bacterial populations or diets to major depressive disorder—leaving open critical questions about the underlying mechanisms of how the gut microbes might influence depression.

Research published last month (May 3) in Cell Metabolism takes an important step toward filling such gaps, demonstrating in multiple animal species that there is likely a causative relationship between depression severity and serum levels of the nonessential amino acid proline, which the study finds depend on both diet and the activity of proline-metabolizing bacteria in the gut.

“To the best of my knowledge, this is the first time that a team actually demonstrates a causal relationship between proline intake and depressive behavior,” King’s College London metabolism researcher Sandrine Claus, who didn’t work on the study and is also chief scientific officer of the microbiome therapeutics company YSOPIA Bioscience, tells The Scientist over email. “I am unaware of a proline-mediated gut-brain axis. This is therefore a completely novel mechanism of action.”

Depression diet: the effects of proline

Previous research had found that proline, among other dietary compounds, seems to play a role in major depressive disorder, but “we found increased levels not only [in] major depression but also in subjects with moderate depression,” study coauthor José Manuel Fernández-Real, a researcher at the Girona Biomedical Research Institute and Dr. Josep Trueta Hospital, both located in Spain, explains. Indeed, the severity of the symptoms correlated with the subjects’ circulating proline.

Fernández-Real and his colleagues uncovered this when they compared people’s responses on an 80-item food intake questionnaire with scores on the Patient Health Questionnaire-9 (PHQ-9), a common clinical survey for diagnosing and measuring the severity of a person’s depression. Out of all the dietary nutrients in the questionnaire, Fernández-Real says, the one “most associated with depressive traits was precisely proline.” Blood tests in the same participants solidified the correlation between proline and depressive traits.

See “Gut Microbes May Play a Role in Mental Health Disorders

However, some discrepancies emerged within the data that demanded a closer look. “Not all subjects with increased proline in the diet had increased proline in the plasma,” hinting that some yet-undiscovered factor was involved, Fernández-Real explains. In search of that explanation, he and the other researchers determined the microbiome compositions of the human participants.

The paper notes that most previous studies attempting to do the same failed to achieve bacterial species-level resolution and have reached inconclusive and conflicting findings. But Fernández-Real and colleagues employed a multi-omics approach that allowed them to link microbial function to the specific biological pathways associated with depression, granting their study a level of resolution that Fernández-Real says was lacking from what he describes as underpowered previous studies.

In the study participants, plasma proline levels were associated with the presence and activity of specific gut bacteria—people with high proline consumption and higher plasma proline levels had different microbiome compositions than those who consumed the same amount of proline but had less circulating in their blood. Furthermore, the team found that the microbial communities of the former were associated with more severe depression.

How the gut microbiome influences depression

To determine whether there’s a direct link between proline and depression, the researchers revisited and modified mouse and Drosophila melanogaster models that they’d previously used to study how the microbiome influenced cognitive abilities.

See “Bacterial Metabolite May Regulate Cognition in Mice

The researchers fed 10 mice a standard diet and another 10 a proline-supplemented diet, then subjected them to stressors typically used to trigger depression-like behaviors. After six weeks, the experimental group had significantly higher proline levels circulating in their plasma and exhibited more signs of depressive behaviors, such as a disinterest in sugar water and decreased mobility during a tail suspension test.

To see how the microbiome factored in, the researchers took fecal samples from 20 human volunteers (nine of whom had high proline levels and all of whom demonstrated a direct correlation between their PHQ-9 score and circulating plasma proline) and put them into antibiotic-treated mice, effectively transferring the human microbiomes into the animals. When the mice were subjected to another test meant to induce depressive behaviors, the researchers found that the mice’s behavior correlated with the PHQ-9 scores—and therefore circulating proline levels—of their donors as well as the mix of microbes now residing in their guts.

The data demonstrated that “a particular microbiota metabolizes proline and is critical to develop more or less depressive symptoms,” says Fernández-Real.

See “Human Gut Microbe Transplant Alters Mouse Behavior

The researchers also conducted RNA sequencing of the animals’ prefrontal cortex, a region of the brain associated with cognition. That revealed that genes related to depressive behaviors had been upregulated following fecal transplantation—and that expression of the proline transporter gene Slc6a20 in the brain correlated with the mice’s behavior and their microbe donors’ PHQ-9 scores.

“The microbiota from subjects with the highest depression scores induced emotional traits in the mice,” says Fernández-Real. “Interestingly, the prefrontal cortex of transplanted mice showed increased expression of genes . . . that we also found in the intestine of subjects with increased proline intake.” 

From there, the researchers moved on to Drosophila experiments, subjecting both wild type control flies and those with downregulated CG43066—the Drosophila version of sl6a20—to stressors to see if the transporters affect whether the animals exhibit depressive behaviors. They then ran the same tests on Drosophila colonized with the bacteria found to increase or decrease proline metabolism in the prior experiments. Downregulating the proline transporter gene or colonizing the Drosophila with specific bacteria, especially certain Lactobacillus species, seemed to protect the flies from depressive behavior, the study found.

Animal depression, human questions

The researchers weren’t able to conduct similar experiments in people, which they concede limits the conclusions that can be drawn from their work. Going forward, Fernández-Real says it will be important to test, for example, “whether diets with different proline contents influence depressive traits and depressive symptomology.”

Chrysi Sergaki, a microbiome researcher at the Medicines & Healthcare products Regulatory Agency in the UK who did not work on the study, tells The Scientist over email that “using these [animal] models is a start. They can help us understand the impact of the microbiome on brain function, but that doesn’t necessarily mean that it will work the same way in humans.” Still, she says that because similar experiments can’t be performed on humans, the animal models used in the new study can grant researchers “a deeper understanding of how the microbiome can influence the functions of the organism they live in,” adding that “that knowledge can be valuable in the way we think about the microbiome when we move to humans.”

See “Distinct Microbiome and Metabolites Linked with Depression

Claus expresses similar sentiments. “Modeling depressive behaviors in animals is . . . very challenging,” she writes. “I actually thought that the drosophila model was interesting despite the fact that we cannot directly translate behavioral observations from drosophila to humans. These are useful to study mechanisms of action though.”

Still, Claus adds that a lack of data on circulating proline levels in the mouse model, combined with repeated reanalysis of the same cohort of people, make it difficult to draw definitive conclusions about the mechanism of microbial proline metabolism and its link to depression.

“The authors keep reanalyzing the same cohort, insisting that they always find a consistent microbial signature with PHQ-9 and proline,” Claus writes. “But this is not surprising since proline is correlated to PHQ-9 score in this cohort, and PHQ-9 score is correlated with a microbial signature.”

Sergaki applauds the study authors for describing the limitations of their work, adding that microbiome studies are notoriously difficult to reproduce and therefore validate. “I think all microbiome scientists look at these studies with a critical eye,” she tells The Scientist. “The authors mention certain limitations of their study which are quite important. The biggest question is always this: correlation or causation? Due to the complexity of the system, this is very difficult to answer.”

Thursday, June 23, 2022

Algorithm could diagnose Alzheimer’s disease from a single brain scan

 reposted from


Algorithm could diagnose Alzheimer’s disease from a single brain scan

Published: 20 June 2022

A single MRI scan of the brain could be enough to diagnose Alzheimer’s disease, according to new research supported by NIHR.

Researchers developed an algorithm to analyse structural features shown on brain MRI scans, including in regions not previously associated with Alzheimer’s. This machine learning technology was able to accurately predict the existence of Alzheimer’s disease and identify the disease at an early stage, when it can be very difficult to diagnose.

Alzheimer’s disease is the most common form of dementia, affecting over half a million people in the UK. Although most people with Alzheimer’s disease develop it after the age of 65, people under this age can develop it too. The most frequent symptoms of dementia are memory loss and difficulties with thinking, problem solving and language.

Currently lots of tests are used to diagnose Alzheimer’s disease, including memory and cognitive tests and brain scans. The scans are used to check for protein deposits in the brain and shrinkage of the hippocampus, the area of the brain linked to memory. All of these tests can take several weeks, both to arrange and to process.

Getting a diagnosis quickly at an early stage helps patients access help and support, get treatment to manage their symptoms, and plan for the future. Being able to accurately identify patients at an early stage of the disease will also help researchers to understand the brain changes that trigger Alzheimer’s disease, and support development and trials of new treatments.

The researchers, supported by Imperial Biomedical Research Centre, studied just one of the tests currently used to diagnose Alzheimer’s disease - an MRI scan. They adapted an algorithm developed for use in classifying cancer tumours and applied it to MRI scans of the brain.

The researchers divided the brain into 115 regions and allocated 660 different features, such as size, shape and texture. They then trained the algorithm to identify where changes to these features could accurately predict the existence of Alzheimer’s disease.

Using data from the Alzheimer’s Disease Neuroimaging Initiative, the team tested their approach on brain scans from over 400 patients with early and later stage Alzheimer’s, healthy controls and patients with other neurological conditions, including frontotemporal dementia and Parkinson’s disease. They also tested it with data from more than 80 patients undergoing diagnostic tests for Alzheimer’s at Imperial College Healthcare NHS Trust.

The research, published in the Nature Portfolio Journal Communications Medicine, found that in 98% of cases, the MRI-based machine learning system alone could accurately predict whether the patient had Alzheimer’s disease or not. It was also able to distinguish between early and late-stage Alzheimer’s with fairly high accuracy, in 79% of patients.

The new system spotted changes in areas of the brain not previously associated with Alzheimer’s disease, including the cerebellum (the part of the brain that coordinates and regulates physical activity) and the ventral diencephalon (linked to the senses, sight and hearing). This opens up potential new avenues for research into these areas and their links to Alzheimer’s disease.

Professor Eric Aboagye, from Imperial’s Department of Surgery and Cancer, who led the research, said: “Currently no other simple and widely available methods can predict Alzheimer’s disease with this level of accuracy, so our research is an important step forward. Many patients who present with Alzheimer’s at memory clinics do also have other neurological conditions, but even within this group our system could pick out those patients who had Alzheimer’s from those who did not.

“Waiting for a diagnosis can be a horrible experience for patients and their families. If we could cut down the amount of time they have to wait, make diagnosis a simpler process, and reduce some of the uncertainty, that would help a great deal. Our new approach could also identify early-stage patients for clinical trials of new drug treatments or lifestyle changes, which is currently very hard to do.”

Dr Paresh Malhotra, who is a consultant neurologist at Imperial College Healthcare NHS Trust and a researcher in Imperial’s Department of Brain Sciences, said: “Although neuroradiologists already interpret MRI scans to help diagnose Alzheimer’s, there are likely to be features of the scans that aren’t visible, even to specialists. Using an algorithm able to select texture and subtle structural features in the brain that are affected by Alzheimer’s could really enhance the information we can gain from standard imaging techniques.”

Read more about this research on the NIHR imperial BRC website

Wednesday, June 15, 2022

Spilling the Tea: Insect DNA Shows Up in World’s Top Beverage

 reposted from


Spilling the Tea: Insect DNA Shows Up in World’s Top Beverage

The Scientist speaks with Trier University’s Henrik Krehenwinkel, whose group recently detected traces of hundreds of arthropod species from a sample of dried plants—in this case, the contents of a tea bag.

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Shawna Williams
Jun 14, 2022
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How do you monitor which species live in an area? In addition to traditional ecological tools such as camera traps, researchers have reported new methods in recent years that allow them to detect minute traces of DNA known as environmental DNA, or eDNA, that animals leave behind in water and even air. In a study published June 15 in Biology Letters, a group reports picking up eDNA from a new source: dried plant material. The team purchased tea from grocery stores, and were able to detect hundreds of species of arthropods in just one bag. 

We asked study coauthor Henrick Krehenwinkel, an ecological geneticist at Trier University in Germany who focuses on the ways in which arthropod communities have changed over time due to human influence, to spill the tea about why his group decided to use eDNA to investigate which critters have been munching on plants. 

TS: Why did you decide in this case to focus on tea? 

Henrik KrehenwinkelWe need [a] time series to understand how insects have changed. When insect decline studies were first published, a lot of people complained [that] there is no real long-term data.  

See “Germany Sees Drastic Decrease in Insects” 

We have a specimen bank here in Trier. They’re collecting leaves from different trees in Germany. They’ve been doing this for 35 years; they go to all kinds of different ecosystems. . . . And what I asked myself is, ‘Couldn’t you also monitor the DNA of the insects which have lived on this leaf?’ . . . We basically did a test experiment where we took these samples, which are frozen in liquid nitrogen, so they’re perfectly stored for DNA preservation . . . and isolated DNA from them, and reconstructed arthropod communities. This is actually another study which is currently in review, where we have basically reconstructed insect community change in German forest ecosystems over the past 35 years.  

So we can extract eDNA from a perfectly frozen leaf. . . . What I asked myself is, “Can you also use other substrates to basically extract the DNA from arthropods?” And is the DNA still stable in other types of substrates? . . . Plant collections in museums, could they actually be useful to understand how insect communities have changed? . . . There are studies saying that . . . if an insect bites into a leaf, it will leave a DNA trace; a little bit of saliva is enough. It’s basically like [how] the criminal breaking into your house, touching your window, will leave their DNA; the insect will leave its DNA when it bites into the leaf. And there are studies saying that this DNA is not very stable, it will be quickly degraded by UV light or washed away by rain. But I was thinking in an herbarium record, the DNA is stored dry and dark, which [are] actually ideal conditions to maintain it.  

Before we started working on herbaria records, we thought we should try something which is kind of comparable to herbarium records. . . . Structure-wise, [tea is] very similar to herbarium record. It’s basically a dried plant which is stored dark and dry. . . . And the DNA should be very stable.  

It’s all driven by our hope to understand insect community change and being able to find new substrates which allow us to travel back in time. . . . You can collect a plant in the field, basically a flower. And you can dry this flower just using silica gel. . . . It’s a substance which is completely harmless, but it’s extremely hydrophilic. . . . If you, for example, put a flower into a little envelope, and then you put it in a Ziploc freezer bag together with a little bit of silica gel, within one day approximately, the flower will be completely dry. . . . And we could in theory even store them at room temperature, we wouldn’t have to worry to put it all in liquid nitrogen or to wash the plant right away . . . you don’t have to carry water in the field, all you need is a little bit of silica gel, an envelope, and a Ziploc bag.  

Another attractive side effect is that what’s very interesting for us ecologists is not only who is at a site, so how many insect species are at a site, . . . but we also want to know how do these insects interact and what do they eat. For example, we know that many insect species are very specific, only living on a certain plant, and when this plant disappears, the insect disappears. . . . Surprisingly, we know very little about these interactions, we know very little about what insect is limited to a certain plant species. We know this pretty well for pest species, but we do not know this pretty well for many other species of insects. . . . And this is a way of very quickly finding this out by basically sampling plant material and being able to associate the insects living on the plant.  

TS: Was there anything about the results of this study that surprised you? 

HK: What really surprised me was the high diversity we detected. . . . We took one tea bag, and . . . I think it was from 100 [or] 150 milligrams of dried plant material, we extracted DNA. And we found in green tea up to 400 species of insects in a single tea bag. . . . That really surprised me. And the reason probably is that this tea, it’s ground to a relatively fine powder. So the eDNA [from all parts of the tea field] gets distributed.  

TS: As far as applying this to herbaria samples, would you need just a relatively small piece of that sample, or could it be an issue that these are rare and very old samples, and you don't want to be grinding up a big chunk of them. 

HK: We’ve been thinking about this, and there’s two options. One is to just very carefully treat the herbarium sample. We’re now testing if you can also just carefully wash the sample, for example, and kind of wash off the traces which are stuck to the sample.  

Then of course, there’s herbaria where they’re actually happy if you do something with them. [H]ere at this university, we have a retired botany professor, and she has very large herbaria she has collected during her tenure. . . . They don’t have a huge scientific value for her, and she would be fine if I grind them up. . . . We’re just testing this, so I cannot give you any results on this yet, but it looks like we are actually able to extract insect DNA out of this as well. . . . And then move back to that same place—she has exact collection sites—I just drive back there, collect the same plant again, and then I can compare how was the insect community 50 years ago when she collected it or 30 years ago when she collected again, and then compare it to how is the insect community on that plant today.  

But of course, generally these collections are very precious and we are developing methods to carefully extract DNA from this without damaging the specimen. This is something we’re just starting now. Seeing how well it worked with tea, I’m now confident that we could also move into other samples like these herbaria. 

TS: Are you a tea drinker yourself? 

HK: I drink coffee actually. . . . And I fear coffee probably is not well suited for it because coffee is roasted. And what DNA really doesn’t like is being heated up to a very high temperature for a long time . . . . We have not tried it yet, but I fear coffee is probably not the best choice for this kind of experiment. 

Editor’s note: This interview has been edited for brevity.

Monday, June 13, 2022

3 ways to boost your memory, according to brain experts

 reposted from CBC radio - thanks Karolina for this one!

3 ways to boost your memory, according to brain experts

From exercise to word games with others, these activities reduce your chances of dementia

A couple dances during the festivities of San Cayetano, the patron saint of labour and bread, in Madrid, Spain, last August. Activities like dance, which combine exercise, socializing and cognition, benefit our brains, a psychologist says. (Andrea Comas/The Associated Press)

Worries about dementia often rank high in polls of Canadians' health concerns, but a neurologist says there are ways to keep our cherished memories strong.

Dr. Sandra Black, a cognitive neurologist at Sunnybrook Health Sciences Centre in Toronto, says with normal aging, short-term memory dulls and the brain's processing speed slows with each decade after 50.

To help counter those declines, Black looks for ways to boost memory that are supported by scientific evidence.

1. Get moving

Exercise, from walking to running, is one memory booster that's backed by more and more research. Canada's guidelines recommend at least 150 minutes of moderate to vigorous physical activity per week for adults.

"When you are aerobically exercising, when you're on that run, your muscles are actually releasing a signal. It's called irisin," Black said. "You're actually stimulating the part of the brain that stores information and learns things."

The recent discovery of the irisin protein builds on other research linking muscle and brain function, Black told Dr. Brian Goldman, host of  CBC's podcast The Dose

Dr. Sandra Black encourages walking and more heart-pumping physical activity as beneficial for mental abilities like memory and language. (Submitted by Sandra Black)

When she sees patients, Black said she talks about why lifestyle choices such as exercise are important. Since a healthy brain needs a lot of oxygen, whatever protects our blood vessels, heart and circulation, also fuels the brain.

Black and other experts encourage walking, or more heart-pumping physical activities, for their benefits to cognitive abilities like memory and language.

2. Eat the good stuff

Black suggests eating a Mediterranean diet rich in green, leafy vegetables like broccoli, kale and cabbage, as well as berries, whole grains, walnuts and fatty fish such as salmon, mackerel and tuna rich in omega-3 fatty acids.

The advice is based on studies that followed people in different populations that seemed to have a lower prevalence of Alzheimer's and vascular disease, compared with populations following other eating patterns.

What else works? In one published clinical trial, researchers showed that medium-chain triglycerides found primarily in coconut oil may help delay worsening Alzheimer's disease compared with taking a sugar pill, the gold standard regulators use to approve medications.

Your best bet is to consume healthy nutrients through a varied diet of mostly whole foods, not supplements that promise those benefits in pill form.

Black said patients who can take supplements aren't told to stop if they can afford them, but her team doesn't endorse them, either. That's because the scientific evidence in favour of many supplements fails to take the placebo effect into account, or the trials weren't long enough to measure an effect, she said.

WATCH | More praise for Mediterranean diet:

More praise for Mediterranean diet

4 years ago
Duration2:26

3. Enjoy word games with others

Penny Pexman, a psychology professor at the University of Calgary who studies cognitive neuroscience, suggests activities that combine exercise, socializing and cognition.

Pexman's lab focuses on how we process language, including a study titled This is your brain on Scrabble

Scrabble players who enjoy the game and its social benefits are motivated to score higher, Pexman said. 

Aside from the social benefits of getting together to play, Pexman's research suggests competitive Scrabble players also recognize words faster than those who didn't routinely put down tiles, particularly for words presented vertically.

"My best recommendation, based on what I know, is to engage in things like dance or pickleball," Pexman said. "You've got things that involve some spatial skills, they're taxing your working memory and they're also giving you social …benefits, too." 

Pickleball is a workout for both spatial skills and working memory that also offers social benefits. (Brian Blanco/The Associated Press Images for Humana)

Why it's not all downhill

Pexman also studies age-related changes, and notes that many, but not all, cognitive abilities start to decline by about age 30. 

"There are things, though, that you can continue to grow," Pexman said. "Your vocabulary grows throughout your life."

Black also points to the wisdom and knowledge we gain with age.

"You have a little more trouble with the word finding, but you know a lot more about the world," Black said. 

A 25-year-old may be faster, but a wise elder in many societies has a richer understanding of culture from their life experience, she added.

ABOUT THE AUTHOR

Amina Zafar

Journalist

Amina Zafar covers medical sciences and health topics, including COVID-19 and other infectious diseases, for CBC News. She holds an undergraduate degree in environmental science and a master's in journalism.