Memory training for the immune system

After an infection of the human body with a pathogen, a cascade of reactions will usually be set into motion. Amongst others, specific cells of the immune system known as T cells get activated in the lymph node and will subsequently divide and proliferate.

At the same time, these cells will gain certain functions, that enable them to destroy other cells, that are e.g. infected by a virus. In addition, they produce certain proteins—so called cytokines—with which they can stop the reproduction of the pathogen.

The immune system and its function are the main focus of the research of Professor Wolfgang Kastenmueller, director of the Chair of Systems Immunology I at the Institute of Systems Immunology of the Julius-Maximiliams-Universität Würzburg (JMU). Together with Professor Georg Gasteiger, director of the Chair of Systems Immunology II, they lead the Max-Planck Research group of Systems Immunology.

Their research focus is the interaction of the immune system with the organism, especially the interaction of different cells of the immune system within local networks and with other cells of other organ systems.

Recently Kastenmueller and his team deciphered new details of the functioning of the immune system, which are important for the immune system to remember recent infections. Their results have been published in the latest issue of the scientific journal Nature Immunology. Their findings could help to improve immune therapy towards tumor diseases.

“If a body has fought and eliminated a pathogen successfully, most of the recently proliferated T cells are no longer needed and will die,” Wolfgang Kastenmueller explains. But about five to ten percent of these cells survive and develop into a long lasting “memory population,” that will protect the body against future infections.

Improvement of the immunological memory

Kastenmueller describes the main result of his study, “In our recent work we identified a transcription factor—BATF3, that very specifically regulates the survival of these cells and therefore the transition into a memory response.” The scientists could show that this factor only gets produced shortly after the initial activation of T cells. The absence of this factor leads to a permanent malfunction of the memory response.

Until now the role of this factor for so-called CD8+ T cells was unclear. It was only after the scientists overexpressed this factor in CD8+ T cells that the importance became clear, as they could see that the survival of these cells and thus the immunological memory improved significantly.

This study was conducted in close collaboration with the Medical Clinic II of the University clinic of Wuerzburg. It combines basic research with applied medicine and could help to develop better therapies for cancer treatments that use the immune system of the patient—so-called CAR-T cell therapy.

Using CAR-T cell therapy, T cells get extracted from the blood of the patient and are subsequently genetically modified with the chimeric antigen receptor (CAR) molecules. This modification enables T cells to attack tumor cells, which they couldn’t biochemically detect before. These modified T cells are subsequently transferred back into the patient.

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How even a short walk can boost your memory

How even a short walk can boost your memory: Exercise improves concentration and problem-solving skills, scientists discover

  • Scientific review found people improved on memory tests after exercising 
  • Findings come from 13 studies which were analysed by Swedish researchers 
  • Exercise is believed to increase levels of a protein called ‘brain-derived neurotrophic factor’ which is thought to be important for memory function

A short walk, run or bike ride could provide a memory boost in less than an hour.

A scientific review looked at people aged 18 to 35 who walked, ran or cycled at moderate to high intensity and then took tests such as remembering a list of 15 words.

The participants, who exercised in bursts of two minutes, or 15 minutes, half an hour or an hour, improved on tests and showed better concentration and problem-solving skills.

The findings come from 13 studies which were analysed by Swedish researchers.

A short walk, run or bike ride could provide a memory boost in less than an hour

The authors, from Jonkoping and Linkoping universities, conclude: ‘This systematic review strongly suggests that aerobic, physical exercise followed by a brief recovery… improves attention, concentration, and learning and memory functions in young adults.’

Exercise is believed to increase levels of a protein called ‘brain-derived neurotrophic factor’ which is thought to be important for memory.

But not everyone is a natural athlete or has hours to work out. 

The review wanted to see if a single bout of exercise could have an effect, so looked at studies exploring this with young adults over ten years.

The review, published in the journal Translational Sports Medicine, found exercise from two minutes to an hour improved memory and thinking skills for up to two hours.

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Good memory to old age – and Why some are long mentally fit – Naturopathy naturopathy specialist portal

Differences in memory performance in old age

Some people show up to a high age has a remarkable memory performance, while others suffer a considerable loss of memory. Now, it was investigated why these differences in memory performance occur in the progressive age and how it can be prevented.

In a study at Stanford University, was to determine which factors have an influence on how well we can remember in old age. The results of the study were published in the English journal “eLife”.

After the memory automatically?

Even in totally healthy people a discount is the end of memory is often an expected part of aging. But such a weakening memory is by no means inevitable. Some people have also in the upscale age is still a very good memory.

Differences in memory performance were investigated

“The study of these differences between individuals is crucial for the understanding of the complexity of brain aging, including the question of how resilience and durability can be promoted,” says study author Alexandra Trelle, at Stanford University, in a press release.

How did the memory retrieval processes of older people?

Based on studies, which had focused on younger people, the research group studied in the framework of the Stanford Aging and Memory Study of memory in healthy, older adults. The Team found that the memory retrieval processes in the brains of older adults can look very similar, as previously in the brains of young adults of the processes observed. In people with greater difficulties to remember, were the instructions on these processes, however, are considerably smaller.

Activity of the whole brain was measured

Through a better understanding of memory function in older adults will one day say, hopefully, earlier and more precise prior allows, when memory failures occur, and when there is an increased risk for dementia is present, report the researchers.

What was studied?

For the study of one hundred part were participants between the ages of 60 and 82 years, their brains using magnetic resonance imaging scanning while they viewed words paired with pictures of famous people and places. These Participants were then testing with words asked during a Memory to recall the associated picture. The analyses of the MRI images of the Gehrins focused not only on the extent of the activity, but also on the memory information contained in the Patterns of brain activity.

What was done the memory test?

With the memory test, the ability should be evaluated, to remember certain associations between elements of an event. This is a Form of memory, which is often influenced disproportionately by the aging process, report researchers.

Memory is a neural time travel

The research group found that the brain processes that support memory in older adults are similar to those in younger groups of the population. If people remember, there is an increase in hippocampal activity, along with the recovery of activity patterns in the cortex, were present when the event was first experienced. This means that the journey includes Remind a quasi-neural time, which includes the Repeat of Patterns that were previously established in the brain.

What has been the role of the Hippo-campus activity?

The Team was able to actually say on the basis of the information contained in Patterns of brain activity to predict whether a Person would remember a specific time or not. The researchers found that memory declined in age, on average. It was noticeable, however, regardless of age, with greater hippocampal activity, and recurrence was associated in the cortex with better memory performance. This was true not only for the during the MRI Scans carried out memory test, but also for memory tests, which were carried out on a different day of the study.

What is the goal of future research?

It is clear that the functional magnetic resonance imaging of brain activity during memory retrieval find stable differences between individuals and on the health of the brain may indicate, reports the researchers. The current study lay the Foundation for many future studies of the memory of older adults in the cohort of the Stanford Aging and Memory Study. The ultimate goal was to develop new and sensitive instruments to identify persons at increased risk for Alzheimer’s disease, before significant memory loss occurs. (as)

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How does the brain link events to form a memory? Study reveals unexpected mental processes

A woman walking down the street hears a bang. Several moments later she discovers her boyfriend, who had been walking ahead of her, has been shot. A month later, the woman checks into the emergency room. The noises made by garbage trucks, she says, are causing panic attacks. Her brain had formed a deep, lasting connection between loud sounds and the devastating sight she witnessed.

This story, relayed by clinical psychiatrist and co-author of a new study Mohsin Ahmed, MD, Ph.D., is a powerful example of the brain’s powerful ability to remember and connect events separated in time. And now, in that new study in mice published today in Neuron, scientists at Columbia’s Zuckerman Institute have shed light on how the brain can form such enduring links.

The scientists uncovered a surprising mechanism by which the hippocampus, a brain region critical for memory, builds bridges across time: by firing off bursts of activity that seem random, but in fact make up a complex pattern that, over time, help the brain learn associations. By revealing the underlying circuitry behind associative learning, the findings lay the foundation for a better understanding of anxiety and trauma- and stressor-related disorders, such as panic and post-traumatic stress disorders, in which a seemingly neutral event can elicit a negative response.

“We know that the hippocampus is important in forms of learning that involve linking two events that happen even up to 10 to 30 seconds apart,” said Attila Losonczy, MD, Ph.D., a principal investigator at Columbia’s Mortimer B. Zuckerman Mind Brain Behavior Institute and the paper’s co-senior author. “This ability is a key to survival, but the mechanisms behind it have proven elusive. With today’s study in mice, we have mapped the complex calculations the brain undertakes in order to link distinct events that are separated in time.”

The hippocampus—a small, seahorse-shaped region buried deep in the brain—is an important headquarters for learning and memory. Previous experiments in mice showed that disruption to the hippocampus leaves the animals with trouble learning to associate two events separated by tens of seconds.

“The prevailing view has been that cells in the hippocampus keep up a level of persistent activity to associate such events,” said Dr. Ahmed, an assistant professor of clinical psychiatry at Columbia’s Vagelos College of Physicians and Surgeons, and co-first author of today’s study. “Turning these cells off would thus disrupt learning.”

To test this traditional view, the researchers imaged parts of the hippocampus of mice as the animals were exposed to two different stimuli: a neutral sound followed by a small but unpleasant puff of air. A fifteen-second delay separated the two events. The scientists repeated this experiment across several trials. Over time, the mice learned to associate the tone with the soon-to-follow puff of air. Using advanced two-photon microscopy and functional calcium imaging, they recorded the activity of thousands of neurons, a type of brain cell, in the animals’ hippocampus simultaneously over the course of each trial for many days.

“With this approach, we could mimic, albeit in a simpler way, the process our own brains undergo when we learn to connect two events,” said Dr. Losonczy, who is also a professor of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons.

To make sense of the information they collected, the researchers teamed up with computational neuroscientists who develop powerful mathematical tools to analyze vast amounts of experimental data.

“We expected to see repetitive, continuous neural activity that persisted during the fifteen-second gap, an indication of the hippocampus at work linking the auditory tone and the air puff,” said computational neuroscientist Stefano Fusi, Ph.D., a principal investigator at Columbia’s Zuckerman Institute and the paper’s co-senior author. “But when we began to analyze the data, we saw no such activity.”

Instead, the neural activity recorded during the fifteen-second time gap was sparse. Only a small number of neurons fired, and they did so seemingly at random. This sporadic activity looked distinctly different from the continuous activity that the brain displays during other learning and memory tasks, like memorizing a phone number.

“The activity appears to come in fits and bursts at intermittent and random time periods throughout the task,” said James Priestley, a doctoral candidate co-mentored by Drs. Losonczy and Fusi at Columbia’s Zuckerman Institute and the paper’s co-first author. “To understand activity, we had to shift the way we analyzed data and use tools designed to make sense of random processes.”

Ultimately, the researchers discovered a pattern in the randomness: a style of mental computing that seems to be a remarkably efficient way that neurons store information. Instead of communicating with each other constantly, the neurons save energy—perhaps by encoding information in the connections between cells, called synapses, rather than through the electrical activity of the cells.

“We were happy to see that the brain doesn’t maintain ongoing activity over all these seconds because, metabolically, that’s not the most efficient way to store information,” said Dr. Fusi, who is also a professor of neuroscience at Columbia’s Vagelos College of Physicians and Surgeons. “The brain seems to have a more efficient way to build this bridge, which we suspect may involve changing the strength of the synapses.”

In addition to helping to map the circuitry involved in associative learning, these findings also provide a starting point to more deeply explore disorders involving dysfunctions in associative memory, such as panic and pos-ttraumatic stress disorder.

“While our study does not explicitly model the clinical syndromes of either of these disorders, it can be immensely informative,” said Dr. Ahmed, who is also a member of the Losonczy lab at Columbia’s Zuckerman Institute. “For example, it can help us to model some aspects of what may be happening in the brain when patients experience a fearful association between two events that would, to someone else, not elicit fright or panic.”

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