The MacDonald home celebrates this Christmas season with a little more excitement than those holidays of the not-so-distant past. My youngest son’s health is the best it’s ever been, and we are in an excellent place. We have nothing to complain about. Life is good and the business of this time of year sparks a fresh sense of hope and joy.
Recently, I shared with a few groups of people the horrors of MacDonald the Younger’s health issues. I discussed how my son could not walk and sat in a wheelchair for more than a solid year. I recounted the many days he spent hospitalized with pain so great that regular pain management regiments could not treat him. We spent more days in the hospital than out.
Why these stories? Why now? My righteous younger dude does not suffer anymore. The only sign he did is a slight limp. Other than that, he is at his prime. There is no obvious reason to discuss these horrible issues anymore. The past is where it should be — in the past. So far, his current medication provides him the protection he needs from breakthrough bleeding. All is well.
After sharing the stories, I usually spend a fair amount of time beating myself up. “Joe, you do not need to share your boy’s struggles. Let it go and get over it.” I’ve continued to keep pouncing on my brain, taking no prisoners. We are in the middle of a time of great health. Why conjure up some of the most challenging times of my life?
One day, while struggling with this thought, a still, small voice inside me seemed to permit my grieving. “Yes,” it said, “Life is incredible right now. The holidays appear fresh and new. There is no reason that you should not take advantage of your newfound health. However, it is also appropriate and human to grieve bad memories.”
I must give myself permission to accept the events of the past and mourn their passing. Acknowledgment gives way to grief, which gives way to healing.
A wave of relief enveloped me as I realized that I needed to give myself space to reflect on the not-so-good moments to appreciate the here and now. Blocking away feelings only prevents me from experiencing the joy that is possible with hard work and self-reflection. The present is heightened with a greater sense of pleasure as I look at the past and turn my attention to the very exciting present. And all it takes is a quick turn of the head.
It is with great joy that the Christmas season began with lights, trees, and an endless array of decorations that tell the stories of our family. We share with gratitude that a season of struggle fades with each passing year and the focus on our current good fortunes allows us to enjoy the holidays like never before. Our memories of the events that held us captive will be with us always, but it will never overshadow the hopes experienced in the here and now. Enjoy this season, this year, at this moment.
We move forward, complete with our whole selves and ready to share with other people struggling to understand the effects of chronic illnesses. They turn to us because we know what it’s like to muddle through the aches and pains associated with medical issues. We stand by caregivers when they feel like there is nothing to do but scream. We remind them of the hope that lies right around the corner. Most of all, we promise never to leave their side. Service to others is where our true healing firmly establishes itself and brings meaning in the middle of our most profound pain.
Having diabetes may affect the way our brains work. Research is taking place to find out exactly how this occurs.
In a recent study, researchers describe how tying diabetes to cognitive impairment is tricky because many people with diabetes have other conditions like high blood pressure and obesity, which also affect cognition. That’s why they conducted a study in young adults with and without type 1 diabetes “who were virtually free of such comorbidities,” the study authors wrote in their abstract.
Christine Embury is a graduate research assistant at the Center for Magnetoencephalography (MEG) at the University of Nebraska Medical Center. She worked with Dr. Wilson, the study’s lead author and was kind enough to answer some questions.
In layman terms, she explains that “neural processing” is brain activity. “In our work, we relate brain activity in specific brain regions to task-specific cognitive processes, like working memory. Widespread brain networks are involved in this kind of complex processing including regions relating to verbal processing and attention, working together to accomplish task goals,” she writes.
Young, Healthy Type 1 Adults Tested
They matched two groups, one with and one without type 1 diabetes, on major health and demographic factors and had them all do a verbal working memory task during magnetoencephalographic (MEG) brain imaging. For the group with type 1 diabetes, the mean years of diabetes duration were only 12.4.
The researchers hypothesized that those with type 1 diabetes would have “altered neural dynamics in verbal working memory processing and that these differences would directly relate to clinical disease measures,” they wrote.
Higher A1c and Diabetes Duration May Alter Brain Activity
They found that those with type 1 diabetes had much stronger neural responses in the superior parietal cortices during memory encoding and much weaker activity in the parietal-occipital regions during maintenance compared to those without type 1 diabetes.
Diabetes duration and glycemic control were both “significantly correlated with neural responses in various brain regions,”
Embury explained that their findings suggest that “the longer one has the condition, the more the brain has to work to compensate for deficits incurred.” Higher A1c levels were also associated with compensatory brain activity, too.
The harrowing conclusion from the study authors is that even young, healthy adults with type 1 diabetes “already have aberrant neural processing relative to their non-diabetic peers, employing compensatory responses to perform the task, and glucose management and duration may play a central role.”
What would be the findings among type 1s who keep their A1c in non-diabetic range, one might wonder? This study suggests it is likely that elevated blood sugar over time is what changes the brain activity. These effects are possibly compounded over time in those with comorbidities like obesity and high blood pressure.
What is Verbal Working Memory?
According to this study, verbal working memory processing may be affected by type 1 diabetes. Embury shared an example of this and wrote, “Participants had to memorize a grid of letters and were later asked to identify if a probe letter was in the previous set of letters shown.” She said we have to use working memory any time that we’re trying to hold on to or manipulate a piece of information for a short amount of time, like remembering a person’s phone number.
The verbal part of “verbal working memory processing” just has to do with the way that the information is presented, like letters or numbers and “anything that requires language processing as well” Embury explains.
More research will help clarify these findings in the future.
For someone who’s not a Sherlock superfan, cognitive neuroscientist Janice Chen knows the BBC’s hit detective drama better than most. With the help of a brain scanner, she spies on what happens inside viewers’ heads when they watch the first episode of the series and then describe the plot.
Chen, a researcher at Johns Hopkins University in Baltimore, Maryland, has heard all sorts of variations on an early scene, when a woman flirts with the famously aloof detective in a morgue. Some people find Sherlock Holmes rude while others think he is oblivious to the woman’s nervous advances. But Chen and her colleagues found something odd when they scanned viewers’ brains: as different people retold their own versions of the same scene, their brains produced remarkably similar patterns of activity1.
Chen is among a growing number of researchers using brain imaging to identify the activity patterns involved in creating and recalling a specific memory. Powerful technological innovations in human and animal neuroscience in the past decade are enabling researchers to uncover fundamental rules about how individual memories form, organize and interact with each other. Using techniques for labelling active neurons, for example, teams have located circuits associated with the memory of a painful stimulus in rodents and successfully reactivated those pathways to trigger the memory. And in humans, studies have identified the signatures of particular recollections, which reveal some of the ways that the brain organizes and links memories to aid recollection. Such findings could one day help to reveal why memories fail in old age or disease, or how false memories creep into eyewitness testimony. These insights might also lead to strategies for improved learning and memory.
The work represents a dramatic departure from previous memory research, which identified more general locations and mechanisms. “The results from the rodents and humans are now really coming together,” says neuroscientist Sheena Josselyn at the Hospital for Sick Children in Toronto, Canada. “I can’t imagine wanting to look at anything else.”
In search of the engram
The physical trace of a single memory — also called an engram — has long evaded capture. US psychologist Karl Lashley was one of the first to pursue it and devoted much of his career to the quest. Beginning around 1916, he trained rats to run through a simple maze, and then destroyed a chunk of cortex, the brain’s outer surface. Then he put them in the maze again. Often the damaged brain tissue made little difference. Year after year, the physical location of the rats’ memories remained elusive. Summing up his ambitious mission in 1950, Lashley wrote2: “I sometimes feel, in reviewing the evidence on the localization of the memory trace, that the necessary conclusion is that learning is just not possible.”
Memory, it turns out, is a highly distributed process, not relegated to any one region of the brain. And different types of memory involve different sets of areas. Many structures that are important for memory encoding and retrieval, such as the hippocampus, lie outside the cortex — and Lashley largely missed them. Most neuroscientists now believe that a given experience causes a subset of cells across these regions to fire, change their gene expression, form new connections, and alter the strength of existing ones — changes that collectively store a memory. Recollection, according to current theories, occurs when these neurons fire again and replay the activity patterns associated with past experience.
Scientists have worked out some basic principles of this broad framework. But testing higher-level theories about how groups of neurons store and retrieve specific bits of information is still challenging. Only in the past decade have new techniques for labelling, activating and silencing specific neurons in animals allowed researchers to pinpoint which neurons make up a single memory (see ‘Manipulating memory’).
Josselyn helped lead this wave of research with some of the earliest studies to capture engram neurons in mice3. In 2009, she and her team boosted the level of a key memory protein called CREB in some cells in the amygdala (an area involved in processing fear), and showed that those neurons were especially likely to fire when mice learnt, and later recalled, a fearful association between an auditory tone and foot shocks. The researchers reasoned that if these CREB-boosted cells were an essential part of the fear engram, then eliminating them would erase the memory associated with the tone and remove the animals’ fear of it. So the team used a toxin to kill the neurons with increased CREB levels, and the animals permanently forgot their fear.
A few months later, Alcino Silva’s group at the University of California, Los Angeles, achieved similar results, suppressing fear memories in mice by biochemically inhibiting CREB-overproducing neurons4. In the process, they also discovered that at any given moment, cells with more CREB are more electrically excitable than their neighbours, which could explain their readiness to record incoming experiences. “In parallel, our labs discovered something completely new — that there are specific rules by which cells become part of the engram,” says Silva.
But these types of memory-suppression study sketch out only half of the engram. To prove beyond a doubt that scientists were in fact looking at engrams, they had to produce memories on demand, too. In 2012, Susumu Tonegawa’s group at the Massachusetts Institute of Technology in Cambridge reported creating a system that could do just that.
By genetically manipulating brain cells in mice, the researchers could tag firing neurons with a light-sensitive protein. They targeted neurons in the hippocampus, an essential region for memory processing. With the tagging system switched on, the scientists gave the animals a series of foot shocks. Neurons that responded to the shocks churned out the light-responsive protein, allowing researchers to single out cells that constitute the memory. They could then trigger these neurons to fire using laser light, reviving the unpleasant memory for the mice5. In a follow-up study, Tonegawa’s team placed mice in a new cage and delivered foot shocks, while at the same time re-activating neurons that formed the engram of a ‘safe’ cage. When the mice were returned to the safe cage, they froze in fear, showing that the fearful memory was incorrectly associated with a safe place6. Work from other groups has shown that a similar technique can be used to tag and then block a given memory7,8.
This collection of work from multiple groups has built a strong case that the physiological trace of a memory — or at least key components of this trace — can be pinned down to specific neurons, says Silva. Still, neurons in one part of the hippocampus or the amygdala are only a tiny part of a fearful foot-shock engram, which involves sights, smells, sounds and countless other sensations. “It’s probably in 10–30 different brain regions — that’s just a wild guess,” says Silva.
A broader brush
Advances in brain-imaging technology in humans are giving researchers the ability to zoom out and look at the brain-wide activity that makes up an engram. The most widely used technique, functional magnetic resonance imaging (fMRI), cannot resolve single neurons, but instead shows blobs of activity across different brain areas. Conventionally, fMRI has been used to pick out regions that respond most strongly to various tasks. But in recent years, powerful analyses have revealed the distinctive patterns, or signatures, of brain-wide activity that appear when people recall particular experiences. “It’s one of the most important revolutions in cognitive neuroscience,” says Michael Kahana, a neuroscientist at the University of Pennsylvania in Philadelphia.
The development of a technique called multi-voxel pattern analysis (MVPA) has catalysed this revolution. Sometimes called brain decoding, the statistical method typically feeds fMRI data into a computer algorithm that automatically learns the neural patterns associated with specific thoughts or experiences. As a graduate student in 2005, Sean Polyn — now a neuroscientist at Vanderbilt University in Nashville, Tennessee — helped lead a seminal study applying MVPA to human memory for the first time9. In his experiment, volunteers studied pictures of famous people, locations and common objects. Using fMRI data collected during this period, the researchers trained a computer program to identify activity patterns associated with studying each of these categories.
Later, as subjects lay in the scanner and listed all the items that they could remember, the category-specific neural signatures re-appeared a few seconds before each response. Before naming a celebrity, for instance, the ‘celebrity-like’ activity pattern emerged, including activation of an area of the cortex that processes faces. It was some of the first direct evidence that when people retrieve a specific memory, their brain revisits the state it was in when it encoded that information. “It was a very important paper,” says Chen. “I definitely consider my own work a direct descendant.”
Chen and others have since refined their techniques to decode memories with increasing precision. In the case of Chen’s Sherlockstudies, her group found that patterns of brain activity across 50 scenes of the opening episode could be clearly distinguished from one another. These patterns were remarkably specific, at times telling apart scenes that did or didn’t include Sherlock, and those that occurred indoors or outdoors.
Near the hippocampus and in several high-level processing centres such as the posterior medial cortex, the researchers saw the same scene-viewing patterns unfold as each person later recounted the episode — even if people described specific scenes differently1. They even observed similar brain activity in people who had never seen the show but had heard others’ accounts of it10.
“It was a surprise that we see that same fingerprint when different people are remembering the same scene, describing it in their own words, remembering it in whatever way they want to remember,” says Chen. The results suggest that brains — even in higher-order regions that process memory, concepts and complex cognition — may be organized more similarly across people than expected.
As new techniques provide a glimpse of the engram, researchers can begin studying not only how individual memories form, but how memories interact with each other and change over time.
At New York University, neuroscientist Lila Davachi is using MVPA to study how the brain sorts memories that share overlapping content. In a 2017 study with Alexa Tompary, then a graduate student in her lab, Davachi showed volunteers pictures of 128 objects, each paired with one of four scenes — a beach scene appeared with a mug, for example, and then a keyboard; a cityscape was paired with an umbrella, and so on. Each object appeared with only one scene, but many different objects appeared with the same scene11. At first, when the volunteers matched the objects to their corresponding scenes, each object elicited a different brain-activation pattern. But one week later, neural patterns during this recall task had become more similar for objects paired with the same scene. The brain had reorganized memories according to their shared scene information. “That clustering could represent the beginnings of learning the ‘gist’ of information,” says Davachi.
Clustering related memories could also help people use prior knowledge to learn new things, according to research by neuroscientist Alison Preston at the University of Texas at Austin. In a 2012 study, Preston’s group found that when some people view one pair of images (such as a basketball and a horse), and later see another pair (such as a horse and a lake) that shares a common item, their brains reactivate the pattern associated with the first pair12. This reactivation appears to bind together those related image pairs; people that showed this effect during learning were better at recognizing a connection later — implied, but never seen — between the two pictures that did not appear together (in this case, the basketball and the lake). “The brain is making connections, representing information and knowledge that is beyond our direct observation,” explains Preston. This process could help with a number of everyday activities, such as navigating an unfamiliar environment by inferring spatial relationships between a few known landmarks. Being able to connect related bits of information to form new ideas could also be important for creativity, or imagining future scenarios.
In a follow-up study, Preston has started to probe the mechanism behind memory linking, and has found that related memories can merge into a single representation, especially if the memories are acquired in close succession13. In a remarkable convergence, Silva’s work has also found that mice tend to link two memories formed closely in time. In 2016, his group observed that when mice learnt to fear foot shocks in one cage, they also began expressing fear towards a harmless cage they had visited a few hours earlier14. The researchers showed that neurons encoding one memory remained more excitable for at least five hours after learning, creating a window in which a partially overlapping engram might form. Indeed, when they labelled active neurons, Silva’s team found that many cells participated in both cage memories.
These findings suggest some of the neurobiological mechanisms that link individual memories into more general ideas about the world. “Our memory is not just pockets and islands of information,” says Josselyn. “We actually build concepts, and we link things together that have common threads between them.” The cost of this flexibility, however, could be the formation of false or faulty memories: Silva’s mice became scared of a harmless cage because their memory of it was formed so close in time to a fearful memory of a different cage. Extrapolating single experiences into abstract concepts and new ideas risks losing some detail of the individual memories. And as people retrieve individual memories, these might become linked or muddled. “Memory is not a stable phenomenon,” says Preston.
Researchers now want to explore how specific recollections evolve with time, and how they might be remodelled, distorted or even recreated when they are retrieved. And with the ability to identify and manipulate individual engram neurons in animals, scientists hope to bolster their theories about how cells store and serve up information — theories that have been difficult to test. “These theories are old and really intuitive, but we really didn’t know the mechanisms behind them,” says Preston. In particular, by pinpointing individual neurons that are essential for given memories, scientists can study in greater detail the cellular processes by which key neurons acquire, retrieve and lose information. “We’re sort of in a golden age right now,” says Josselyn. “We have all this technology to ask some very old questions.”
In two independent studies, scientists at the University of Basel have demonstrated that both the structure of the brain and several memory functions are linked to immune system genes. The scientific journals Nature Communications and Nature Human Behaviour have published the results of the research.
The body’s immune system performs essential functions, such as defending against bacteria and cancer cells. However, the human brain is separated from immune cells in the bloodstream by the so-called blood-brain barrier. This barrier protects the brain from pathogens and toxins circulating in the blood, while also dividing the immune cells of the human body into those that fulfill their function in the blood and those that work specifically in the brain. Until recently, it was thought that brain function was largely unaffected by the peripheral immune system.
However, in the past few years, evidence has accumulated to indicate that the blood’s immune system could in fact have an impact on the brain. Scientists from the University of Basel’s Transfaculty Research Platform Molecular and Cognitive Neurosciences (MCN) have now carried out two independent studies that demonstrate that this link between the immune system and brain is more significant than previously believed.
Search for regulatory patterns
In the first study, the researchers searched for epigenetic profiles, i.e. regulatory patterns, in the blood of 533 young, healthy people. In their genome-wide search, they identified an epigenetic profile that is strongly correlated with the thickness of the cerebral cortex, in particular in a region of the brain that is important for memory functions. This finding was confirmed in an independent examination of a further 596 people. It also showed that it is specifically those genes that are responsible for the regulation of important immune functions in the blood that explain the link between the epigenetic profile and the properties of the brain.
Gene variant intensifies traumatic memories
In the second study, the researchers investigated the genomes of healthy participants who remembered negative images particularly well or particularly poorly. A variant of the TROVE2 gene, whose role in immunological diseases is currently being investigated, was linked to participants’ ability to remember a particularly high number of negative images, while their general memory remained unaffected.
This gene variant also led to increased activity in specific regions of the brain that are important for the memory of emotional experiences. The researchers also discovered that the gene is linked to the strength of traumatic memories in people who have experienced traumatic events.
The results of the two studies show that both brain structure and memory are linked to the activity of genes that also perform important immune regulatory functions in the blood. “Although the precise mechanisms behind the links we discovered still need to be clarified, we hope that this will ultimately lead to new treatment possibilities,” says Professor Andreas Papassotiropoulos, Co-Director of the University of Basel’s MCN research platform. The immune system can be precisely affected by certain medications, and such medications could also have a positive effect on impaired brain functions.
Innovative research methods
These groundbreaking findings were made possible thanks to cutting edge neuroscientific and genetic methods at the University of Basel’s MCN research platform. Under the leadership of Professor Andreas Papassotiropoulos and Professor Dominique de Quervain, the research platform aims to help us better understand human brain functions and to develop new treatments for psychiatric disorders.
Many Europeans believe in the benefits of napping so much that they shut down in the afternoon to allow everyone to take a quick power nap, recharge, and come back to work.
Unfortunately, this isn’t the case in the U.S. where a mid-day nap is not only a luxury, but often times is perceived as downright laziness.
If you’re among those who enjoy the occasional midday snooze, you should continue the habit as studies have shown that it’s a normal and integral part of the circadian (sleep-wake cycle) rhythm.
Studies have shown that short naps can improve awareness and productivity. You don’t need much; just 15 to 20 minutes can make a world of difference.
According to a study from the University of Colorado Boulder discovered that children who didn’t take their afternoon nap didn’t display much joy and interest, had a higher level of anxiety, and lower problem solving skills compared to other children who napped regularly. The same goes for adults as well. Researchers with Berkeley found that adults who regularly take advantage of an afternoon nap have a better learning ability and improved memory function. Why is napping so essential? Because it gives your brain a reboot, where the short-term memory is cleared out and our brain becomes refreshed with new defragged space.
How long should you nap?
According to experts, 10 to 20 minutes is quite enough to refresh your mind and increase your energy and alertness. The sleep isn’t as deep as longer naps and you’re able to get right back at your day immediately after waking up. If you nap for 30 minutes you may deal with a 30-minute grogginess period because you wake up just as your body started entering a deeper stage of sleep. The same can be said if you sleep for an hour, but on the other hand, these 60-minute naps provide an excellent memory boost. The longest naps— lasting about 90 minutes—are recommended for those people who just don’t get enough sleep at night. Since it’s a complete sleep cycle, it can improve emotional memory and creativity.
There you have it – naps are good for you physical and mental well being so you should practice them as much as you can. However, be advised that you shouldn’t sacrifice nighttime sleeping for an afternoon nap, they should be an addition to a good night sleep.
UNIVERSITY OF EDINBURGH — Brain connections that play a key role in complex thinking skills show the poorest health with advancing age, new research suggests.
Connections supporting functions such as movement and hearing are relatively well preserved in later life, the findings show.
Scientists carrying out the most comprehensive study to date on ageing and the brain’s connections charted subtle ways in which the brain’s connections weaken with age.
Knowing how and where connections between brain cells – so-called white matter – decline as we age is important in understanding why some people’s brains and thinking skills age better than others.
Worsening brain connections as we age contribute to a decline in thinking skills, such as reasoning, memory and speed of thinking.
Researchers from the University of Edinburgh analysed brain scans from more than 3,500 people aged between 45 and 75 taking part in the UK Biobank study.
Researchers say the data will provide more valuable insights into healthy brain and mental ageing, as well as making contributions to understanding a range of diseases and conditions.
The study was published in Nature Communications journal.
Dr Simon Cox, of the University of Edinburgh’s Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), who led the study, said: “By precisely mapping which connections of the brain are most sensitive to age, and comparing different ways of measuring them, we hope to provide a reference point for future brain research in health and disease.
“This is only one of the first of many exciting brain imaging results still to come from this important national health resource.”
Professor Ian Deary, Director of CCACE, said: “Until recently, studies of brain scans with this number of people were not possible. Day by day the UK Biobank sample grows, and this will make it possible to look carefully at the environmental and genetic factors that are associated with more or less healthy brains in older age.”
Professor Paul Matthews of Imperial College London, Chair of the UK Biobank Expert Working Group, who was not involved in the study, said: “This report provides an early example of the impact that early opening of the growing UK Biobank Imaging Enhancement database for access by researchers world-wide will have.
“The large numbers of subjects in the database has enabled the group to rapidly characterise the ways in which the brain changes with age – and to do so with the confidence that large numbers of observations allow.
“This study highlights the feasibility of defining what is typical, to inform the development of quantitative MRI measures for decision making in the clinic.”
The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology receives funding from the Medical Research Council (MRC) and the Biotechnology and Biological Sciences Research Council (BBSRC).
UK Biobank was established by the Wellcome Trust, MRC, Department of Health, Scottish Government and the Northwest Regional Development Agency. It has had funding from the Welsh Assembly Government, British Heart Foundation and Diabetes UK. UK Biobank is hosted by the University of Manchester and supported by the NHS.
A video explanation of the research is available at: http://www.ccace.ed.ac.uk/news-events/latest
Memory loss in mice has been successfully reversed following the discovery of new information about a key mechanism underlying the loss of nerve connectivity in the brain, say UCL researchers.
Published today in Current Biology, the study funded by Alzheimer’s Research UK, Parkinson’s UK, Wellcome, MRC and the EU investigated the mechanism driving communication breakdown in adult brains – specifically, the loss of connections between nerve cells in the hippocampus, an area of the brain that controls learning and memory. The team found Wnt proteins play a key role in the maintenance of nerve connectivity in the adult brain and could become targets for new treatments that prevent and restore brain function inneurodegenerative diseases.
The breakdown of connections between nerve cells is an early feature of diseases like Alzheimer’s and is known to cause distressing symptoms like memory and thinking decline, but the biological processes behind it are poorly understood. Nerve cells are connected at communication points called synapses and the slow degeneration of these connections is an important area of study for researchers looking to slow or stop Alzheimer’s disease.
Lead author, Professor Patricia Salinas (UCL Cell & Developmental Biology), said: “Synapses are absolutely critical to everything that our brains do. When these important communication points are lost, nerve cells cannot exchange information and this leads to symptoms like memory and thinking problems. The Wnt pathway is emerging as a key player in the regulation of the formation, maintenance and function of synapses, and we have provided strong evidence that the Wnt proteins are also critical for memory.
“Understanding the role of Wnts in Alzheimer’s disease is an important next step, as there is potential we could target this chain of events with drugs. Preventing or reversing the disruptions in connectivity and communication between nerve cells in Alzheimer’s would be a huge step forward.”
Increasing evidence suggests that deficiency in Wnt function contributes to disruption of brain connectivity in Alzheimer’s disease and therefore resulting in memory loss. The team studied the impact of a protein called Dkk1, known to block the action of Wnts and found at higher levels in people with Alzheimer’s, in brain circuits and memory.
Genetically modified mice in which Dkk1 can be switched on, disrupting the action of Wnts and its downstream chain of events were used. To avoid any disruption to normal brain development driven by Wnts and Dkk1, the researchers waited until the mice were adults before switching on Dkk1 in an area of the brain important for the formation of new memories.
When Dkk1 was switched on in the adult mice, the researchers found the mice had memory problems, and that this coincided with the presence of fewer synapses between nerve cells, indicating a communication breakdown. However, when the researchers switched Dkk1 back off, the mice no longer had memory problems, the number of synapses increased back to normal levels and brain circuits were restored.
Dr Simon Ridley, Director of Research at Alzheimer’s Research UK, said: “This study in mice adds further weight to a growing body of evidence implicating Wnts and its related proteins to nerve cell connectivity and memory. By understanding mechanisms driving healthy nerve cells, we can best unpick what happens when these processes go so wrong.
“This research sets a solid foundation for future work to explore the role of Wnts in diseases like Alzheimer’s, and this biological process is already a key target being explored by expert teams in the Alzheimer’s Research UK Drug Discovery Alliance. Researchers are taking huge steps forward in their understanding of what happens in the brain in health and disease, and we must now capitalise on these discoveries to deliver effective treatments that can transform lives.”
Researchers from the Universities of Groningen (Netherlands) and Pennsylvania have discovered a piece in the puzzle of how sleep deprivation negatively affects memory.
For the first time, a study in mice, to be published in the journal eLife, shows that five hours of sleep deprivation leads to a loss of connectivity between neurons in the hippocampus, a region of the brain associated with learning and memory.
“It’s clear that sleep plays an important role in memory – we know that taking naps helps us retain important memories. But how sleep deprivation impairs hippocampal function and memory is less obvious,” says first author Robbert Havekes, PhD, Assistant Professor at the Groningen Institute for Evolutionary Life Sciences.
It has been proposed that changes in the connectivity between synapses – structures that allow neurons to pass signals to each other – can affect memory. To study this further, the researchers examined the impact of brief periods of sleep loss on the structure of dendrites, the branching extensions of nerve cells along which impulses are received from other synaptic cells, in the mouse brain.
They first used the Golgi silver-staining method to visualize the length of dendrites and number of dendritic spines in the mouse hippocampus following five hours of sleep deprivation, a period of sleep loss that is known to impair memory consolidation. Their analyses indicated that sleep deprivation significantly reduces the length and spine density of the dendrites belonging to the neurons in the CA1 region of the hippocampus.
They repeated the sleep-loss experiment, but left the mice to sleep undisturbed for three hours afterwards. This period was chosen based on the scientists’ previous work showing that three hours is sufficient to restore deficits caused by lack of sleep. The effects of the five-hour sleep deprivation in the mice were reversed so that their dendritic structures were similar to those observed in the mice that had slept.
The researchers then investigated what was happening during sleep deprivation at the molecular level. “We were curious about whether the structural changes in the hippocampus might be related to increased activity of the protein cofilin, since this can cause shrinkage and loss of dendritic spines,” Havekes says.
“Our further studies revealed that the molecular mechanisms underlying the negative effects of sleep loss do in fact target cofilin. Blocking this protein in hippocampal neurons of sleep-deprived mice not only prevented the loss of neuronal connectivity, but also made the memory processes resilient to sleep loss. The sleep-deprived mice learned as well as non-sleep deprived subjects.”
Ted Abel, PhD, Brush Family Professor of Biology at the University of Pennsylvania and senior author of the study, explains: “Lack of sleep is a common problem in our 24/7 modern society and it has severe consequences for health, overall wellbeing, and brain function.
“Despite decades of research, the reasons why sleep loss negatively impacts brain function have remained unknown. Our novel description of a pathway through which sleep deprivation impacts memory consolidation highlights the importance of the neuronal cell network’s ability to adapt to sleep loss. What is perhaps most striking is that these neuronal connections are restored with several hours of recovery sleep. Thus, when subjects have a chance to catch up on much-needed sleep, they are rapidly remodeling their brain.”