Posts tagged memory

June 4, 2012

In a new study of the effects of soy supplements for postmenopausal women, researchers at the Stanford University School of Medicine and the USC Keck School of Medicine found no significant differences — positive or negative — in overall mental abilities between those who took supplements and those who didn’t.

While questions have swirled for years around a possible link between soy consumption and changes in cognition, this research offers no evidence to support such claims. “There were no large effects on overall cognition one way or another,” said the study’s lead author, Victor Henderson, MD, professor of health research and policy and of neurology and neurological sciences at Stanford.

The findings from the 2.5-year study in middle-aged and older women, which was larger and longer than any previous trials on soy use, will appear in the June 5 issue of Neurology, the medical journal of the American Academy of Neurology. The results are in line with the largest previous study in this area: a 12-month trial of Dutch women during which daily soy intake showed “no significant effect on cognitive endpoints.” That work was published in a 2004 issue of the Journal of the American Medical Association.

Still, there are a number of randomized clinical trials on soy’s effect on cognition and memory in women that have presented conflicting takes about its benefits and harms. While improved cognition was seen in some findings, other research suggested that soy could have an adverse effect on memory.

Soy and soy-based products contain an estrogen-like compound called isoflavones, and some women choose to take soy supplements as an alternative to estrogen. It has been thought that isoflavones might be able to boost memory and perhaps overall brain function. The hippocampus, the part of the brain that controls memory, is rich in estrogen beta receptors, and isoflavones are known to activate these receptors.

Henderson’s interest in the matter is part of his broader research agenda on finding new strategies to improve cognitive function in aging.

For this work, he and his colleagues conducted the National Institutes of Health-sponsored Women’s Isoflavone Soy Health Trial, which was done between 2004 and 2008 to determine the effect of soy isoflavones on the progression of atherosclerosis and, secondarily, the effect on cognition. During this study, 350 healthy women ages 45-92 were randomized to receive daily 25 grams of isoflavone-rich soy protein (a dose comparable to that of traditional Asian diets) or a placebo. A battery of neuropsychological tests was given to the participants at the start of the study and again 2.5 years later.

Henderson and his colleagues examined changes to the composite of 14 scores and found no significant differences in global cognition — that is, overall mental abilities — from baseline to study-end between women who took the supplements and those on placebo. During a planned secondary analysis, they did identify a statistically significant difference in one of the identified cognitive factors: Women in the supplement group showed a greater improvement in visual memory (memory for faces). Henderson said this could be important, but “the finding needs to be replicated in future studies.”

According to Henderson, this research “helps provide a firm answer” about soy and overall cognition, and he and his co-authors note in the paper that postmenopausal women shouldn’t pursue a high-soy diet or take supplements for the primary goal of global cognitive benefit.

At the same time, Henderson said the work is not meant discourage women who consume soy for other purposes. “I don’t think they should be disappointed at all,” he said. “They should be pleased that there aren’t negative effects on overall cognitive function and that there are potential gains in aspects of memory. If a woman enjoys eating soy and if there may be other health benefits, she should keep doing what she’s doing.”

The researchers note that while these results are reasonably definitive — Henderson said the sample size was large enough that if there were major effects, the researchers would have likely seen them — the cognitive effects of soy isoflavones might differ for women of reproductive age and for men. More study is needed in these populations, he said. He also emphasized the need for researchers to continue studying a variety of interventions to improve cognition among older adults, including nutritional approaches, physical and mental activities, and pharmaceutical approaches.

Journal reference: Neurology

Source: medicalxpress.com

ScienceDaily (May 31, 2012) — Working memory training is unlikely to be an effective treatment for children suffering from disorders such as attention-deficit/hyperactivity or dyslexia, according to a research analysis published by the American Psychological Association. In addition, memory training tasks appear to have limited effect on healthy adults and children looking to do better in school or improve their cognitive skills.

"The success of working memory training programs is often based on the idea that you can train your brain to perform better, using repetitive memory trials, much like lifting weights builds muscle mass," said the study’s lead author, Monica Melby-Lervåg, PhD, of the University of Oslo. "However, this analysis shows that simply loading up the brain with training exercises will not lead to better performance outside of the tasks presented within these tests." The article was published online in Developmental Psychology.

Working memory enables people to complete tasks at hand by allowing the brain to retain pertinent information temporarily. Working memory enhancing tasks usually involve trying to get people to remember information presented to them while they are performing distracting activities. For example, participants may be presented with a series of numbers one at a time on a computer screen. The computer presents a new digit and then prompts participants to recall the number immediately preceding. More difficult versions might ask participants to recall what number appeared two, three or four digits ago.

In this meta-analysis, researchers from the University of Oslo and University College London examined 23 peer-reviewed studies with 30 different comparisons of groups that met their criteria. The studies were randomized controlled trials or experiments, had some sort of working memory treatment and a control group. The studies comprised a wide range of participants, including young children, children with cognitive impairments, such as ADHD, and healthy adults. Most of the studies had been published within the last 10 years.

Overall, working memory training improved performance on tasks related to the training itself but did not have an impact on more general cognitive performance such as verbal skills, attention, reading or arithmetic. “In other words, the training may help you improve your short-term memory when it’s related to the task implemented in training but it won’t improve reading difficulties or help you pay more attention in school,” said Melby-Lervåg.

In recent years, several commercial, computer-based working memory training programs have been developed and purport to benefit students suffering from ADHD, dyslexia, language disorders, poor academic performance or other issues. Some even claim to boost people’s IQs. These programs are widely used around the world in schools and clinics, and most involve tasks in which participants are given many memory tests that are designed to be challenging, the study said.

"In the light of such evidence, it seems very difficult to justify the use of working memory training programs in relation to the treatment of reading and language disorders," said Melby-Lervåg. "Our findings also cast strong doubt on claims that working memory training is effective in improving cognitive ability and scholastic attainment."

Source: Science Daily

May 22, 2012

(Medical Xpress) — Researchers at the Institut Pasteur and the CNRS have recently identified in mice the role played by neo-neurons formed in the adult brain. By using selective stimulation the researchers were able to show that these neo-neurons increase the ability to learn and memorize difficult cognitive tasks. This newly discovered characteristic of neo-neurons to assimilate complex information could open up new avenues in the treatment of some neurodegenerative diseases. This publication is available online on the Nature Neuroscience journal’s website.

Section of a mouse brain observed using a fluorescence microscope. The green filaments represent neo-neurons in an organized network. Credit: Institut Pasteur

The discovery that new neurons could be formed in the adult brain created quite a stir in 2003 by debunking the age-old belief that a person is born with a set number of neurons and that any loss of neurons is irreversible. This discovery was all the more incredible considering that the function of these new neurons remained undetermined. That is, until today.

Using mice models the team working under Pierre-Marie Lledo, head of the Laboratory for Perception and Memory (Institut Pasteur/CNRS) recently revealed the role of these neo-neurons formed in the adult brain with respect to learning and memory. With the help of an experimental approach using optogenetics, developed by this very same team and published in December 2010, the researchers were able to show that when stimulated by a brief flash of light these neo-neurons facilitate both learning and the memorization of complex tasks. This resulted in mice models that were able to memorize information given during the learning activity more quickly and remember exercises even 50 days after experimentation had ended. The study also shows that neo-neurons generated just after birth hold no added advantages as relates to either learning or memory. In this respect it is only the neurons produced by the adult brain that have any considerable significance.

“This study shows that the activity of just a few neurons produced in the adult brain can still have considerable effects on cognitive processes and behavior. Moreover, this work helps to illustrate how the brain assimilates new stimulations seeing as normally electrical activity (which we mimic using flashes of light) is produced within the brain’s attention centers”, explains the study’s director Pierre-Marie Lledo.

Beyond simply discovering the functional contribution of these neo-neurons, the study has also reaffirmed the clear link between “mood” (defined here by a specific pattern of stimulation) and cerebral activity. It has been shown that curiosity, attentiveness and pleasure all promote the formation of neo-neurons and consequently the acquisition of new cognitive abilities. Conversely, a state of depression is detrimental to the production of new neurons and triggers a vicious cycle which prolongs this state of despondency. These results, and the optogenetics technologies that enabled this study, may prove very useful for devising therapeutic protocols which aim to counter the development of neurologic or psychiatric diseases.

Provided by CNRS

Source: medicalxpress.com

ScienceDaily (May 15, 2012) — Attention, college students cramming between midterms and finals: Binging on soda and sweets for as little as six weeks may make you stupid.

New research suggests that binging on soda and sweets for as little as six weeks may make you stupid. (Credit: © RTimages / Fotolia)

A new UCLA rat study is the first to show how a diet steadily high in fructose slows the brain, hampering memory and learning — and how omega-3 fatty acids can counteract the disruption. The peer-reviewed Journal of Physiology publishes the findings in its May 15 edition.

"Our findings illustrate that what you eat affects how you think," said Fernando Gomez-Pinilla, a professor of neurosurgery at the David Geffen School of Medicine at UCLA and a professor of integrative biology and physiology in the UCLA College of Letters and Science. "Eating a high-fructose diet over the long term alters your brain’s ability to learn and remember information. But adding omega-3 fatty acids to your meals can help minimize the damage."

While earlier research has revealed how fructose harms the body through its role in diabetes, obesity and fatty liver, this study is the first to uncover how the sweetener influences the brain.

The UCLA team zeroed in on high-fructose corn syrup, an inexpensive liquid six times sweeter than cane sugar, that is commonly added to processed foods, including soft drinks, condiments, applesauce and baby food. The average American consumes more than 40 pounds of high-fructose corn syrup per year, according to the U.S. Department of Agriculture. “We’re not talking about naturally occurring fructose in fruits, which also contain important antioxidants,” explained Gomez-Pinilla, who is also a member of UCLA’s Brain Research Institute and Brain Injury Research Center. “We’re concerned about high-fructose corn syrup that is added to manufactured food products as a sweetener and preservative.”

Gomez-Pinilla and study co-author Rahul Agrawal, a UCLA visiting postdoctoral fellow from India, studied two groups of rats that each consumed a fructose solution as drinking water for six weeks. The second group also received omega-3 fatty acids in the form of flaxseed oil and docosahexaenoic acid (DHA), which protects against damage to the synapses — the chemical connections between brain cells that enable memory and learning.

"DHA is essential for synaptic function — brain cells’ ability to transmit signals to one another," Gomez-Pinilla said. "This is the mechanism that makes learning and memory possible. Our bodies can’t produce enough DHA, so it must be supplemented through our diet."

The animals were fed standard rat chow and trained on a maze twice daily for five days before starting the experimental diet. The UCLA team tested how well the rats were able to navigate the maze, which contained numerous holes but only one exit. The scientists placed visual landmarks in the maze to help the rats learn and remember the way.

Six weeks later, the researchers tested the rats’ ability to recall the route and escape the maze. What they saw surprised them.

"The second group of rats navigated the maze much faster than the rats that did not receive omega-3 fatty acids," Gomez-Pinilla said. "The DHA-deprived animals were slower, and their brains showed a decline in synaptic activity. Their brain cells had trouble signaling each other, disrupting the rats’ ability to think clearly and recall the route they’d learned six weeks earlier."

The DHA-deprived rats also developed signs of resistance to insulin, a hormone that controls blood sugar and regulates synaptic function in the brain. A closer look at the rats’ brain tissue suggested that insulin had lost much of its power to influence the brain cells.

"Because insulin can penetrate the blood-brain barrier, the hormone may signal neurons to trigger reactions that disrupt learning and cause memory loss," Gomez-Pinilla said.

He suspects that fructose is the culprit behind the DHA-deficient rats’ brain dysfunction. Eating too much fructose could block insulin’s ability to regulate how cells use and store sugar for the energy required for processing thoughts and emotions.

"Insulin is important in the body for controlling blood sugar, but it may play a different role in the brain, where insulin appears to disturb memory and learning," he said. "Our study shows that a high-fructose diet harms the brain as well as the body. This is something new."

Gomez-Pinilla, a native of Chile and an exercise enthusiast who practices what he preaches, advises people to keep fructose intake to a minimum and swap sugary desserts for fresh berries and Greek yogurt, which he keeps within arm’s reach in a small refrigerator in his office. An occasional bar of dark chocolate that hasn’t been processed with a lot of extra sweetener is fine too, he said.

Still planning to throw caution to the wind and indulge in a hot-fudge sundae? Then also eat foods rich in omega-3 fatty acids, like salmon, walnuts and flaxseeds, or take a daily DHA capsule. Gomez-Pinilla recommends one gram of DHA per day.

"Our findings suggest that consuming DHA regularly protects the brain against fructose’s harmful effects," said Gomez-Pinilla. "It’s like saving money in the bank. You want to build a reserve for your brain to tap when it requires extra fuel to fight off future diseases."

Source: Science Daily

May 10, 2012

(Medical Xpress) — How do we build a memory in the brain? It is well known that for animals (and humans) new proteins are needed to establish long-term memories. During learning information is stored at the synapses, the junctions connecting nerve cells. Synapses also require new proteins in order to show changes in their strength (synaptic plasticity). Historically, scientists have focused on the cell body as the place where the required proteins are synthesized. However, in recent years there has been increasing focus on the dendrites and axons (the compartments that meet to form synapses) as a potential site for protein synthesis.

Protein synthesis machines have been observed there as well as a limited number of their templates, the messenger RNA molecules. The limited number of mRNAs observed in dendrites and axons placed constraints on the constellation of proteins that could be synthesized to help synapses work and change. Researchers from Erin Schuman’s lab at the Max Planck Institute (MPI) for Brain Research used new-generation sequencing to directly identify a very large number (over 2500) of new mRNA molecules that are present at the axons and dendrites. Using high-resolution imaging techniques they were able to both quantify and visualize individual mRNA molecules. They published their findings in the latest issue of Neuron.

[Video]
Erin Schuman and her colleagues describe how they were able to detect numerous new mRNAs in the processes of neurons with unprecedented sensitivity. Video: Neuron.

Using microarray approaches and/or in situ hybridization techniques, many different groups had each identified a hundred or so mRNAs that might reside in the dendrites. By analyzing and comparing these studies the Schuman team discovered something surprising: it seems that not a single mRNA type was found in all three studies. This observation made the scientist at the MPI for Brain Research wonder whether the already discovered mRNAs are just the tip of the iceberg and whether there were many more mRNA molecules waiting to be discovered.

In order to find out the researchers dissected the neuropil layer of the rat hippocampus. This layer comprises a high concentration of axons and dendrites, but lacks the cell bodies of pyramidal neurons (the principal cell type in the hippocampus and other brain areas). By using sensitive high-resolution sequencing techniques, mRNAs could be detected which, due to their lower concentrations, were not discovered before. The researchers found an impressive number of 2550 unique mRNAs present at the dendrites and/or axons. To determine the relative abundance in the neuronal cells, the scientists at Erin Schuman’s lab used the Nanostring nCounter, a new technique allowing the high-resolution visualization and quantification of single mRNA molecules. They found that the concentration of mRNAs in the euronal cells varies by three orders of magnitude. Additionally, the researchers were able to classify many of the mRNAs and determine their function in synaptic plasticity. These include signaling molecules, scaffolds and the receptors for neurotransmitter molecules. In addition, many mRNAs coding for protein implicated in diseases like autism were discovered in the dendrites and axons. Finally, by using advanced imaging techniques, the researchers could directly visualize some of the mRNAs in the neuronal dendrites, hundreds of micrometers from the cell body.

These results reveal a previously unappreciated enormous potential for the local protein synthesis machinery to supply, maintain and modify the dendritic and synaptic protein population. It seems that neurons use a local control mechanism much in the same way that modern societies have learned that the most efficient means to distribute goods to the population is to use local distribution centers.

Provided by Max Planck Society

Source: medicalxpress.com

May 9, 2012

Research published in the May 10 issue of the journal Neuron, describes a potential new therapeutic approach for improving memory and modifying disease progression in patients with amnestic mild cognitive impairment. The study finds that excess brain activity may be doing more harm than good in some conditions that cause mild cognitive decline and memory impairment.

Elevated activity in specific parts of the hippocampus, a brain region involved in memory, is often seen in disorders associated with an increased risk for Alzheimer’s disease. Amnestic mild cognitive impairment (aMCI), where memory is worse than would be expected for a person’s age, is one such disorder. “In the case of early aMCI, it has been suggested that the increased hippocampal activation may serve a beneficial function by recruiting additional neural resources to compensate for those that are lost,” explains senior study author, Dr. Michela Gallagher, from Johns Hopkins University. “However, animal studies have raised the alternative view that this excess activation may be contributing to memory impairment.”

Dr. Gallagher and colleagues tested how a reduction of hippocampal activity would impact human patients with aMCI. The researchers used a low dose of a drug used clinically to treat epilepsy, for the purpose of reducing hippocampal activity in subjects with aMCI to levels that were similar to activity levels in healthy, age-matched subjects in a control group. The researchers found that treatment with the drug improved performance on a memory task. These findings point to the therapeutic potential of reducing excess activation in the hippocampus in aMCI.

The results also have broader significance as elevated activity in the hippocampus is also observed in other conditions that are thought to precede Alzheimer’s disease, and may be one of the underlying mechanisms of neurodegeneration. “Apart from a direct role in memory impairment, there is concern that elevated activity in vulnerable neural networks could be causing additional damage and, possibly, widespread disease-related degeneration that underlies cognitive decline and the conversion to Alzheimer’s disease,” concludes Dr. Gallagher. “Therefore, reducing the elevated activity in the hippocampus may help to restore memory and protect the brain.”

Provided by Cell Press

More information: Bakker et al.: “Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment.”,DOI:10.1016/j.neuron.2012.03.023

Source: medicalxpress.com

ScienceDaily (May 8, 2012) — Whether it’s a line from a movie, an advertising slogan or a politician’s catchphrase, some statements take hold in people’s minds better than others. But why?

Cornell researchers who applied computer analysis to a database of movie scripts think they may have found the secret of what makes a line memorable.

The study suggests that memorable lines use familiar sentence structure but incorporate distinctive words or phrases, and they make general statements that could apply elsewhere. The latter may explain why lines such as, “You’re gonna need a bigger boat” or “These aren’t the droids you’re looking for” (accompanied by a hand gesture) have become standing jokes. You can use them in a different context and apply the line to your own situation.

While the analysis was based on movie quotes, it could have applications in marketing, politics, entertainment and social media, the researchers said.

"Using movie scripts allowed us to study just the language, without other factors. We needed a way of asking a question just about the language, and the movies make a very nice dataset," said graduate student Cristian Danescu-Niculescu-Mizil, first author of a paper to be presented at the 50th Annual Meeting of the Association for Computational Linguistics July 8-14 in Jeju, South Korea.

The study grows out of ongoing work on how ideas travel across networks.

"We’ve been looking at things like who talks to whom," said Jon Kleinberg, a professor of computer science who worked on the study, "but we hadn’t explored how the language in which an idea was presented might have an effect."

To address that, they collaborated with Lillian Lee, a professor of computer science who specializes in computer processing of natural human language.

They obtained scripts from about 1,000 movies, and a database of memorable quotes from those movies from the Internet Movie Database. Each quote was paired with another from the movie’s script, spoken by the same character in the same scene and about the same length, to eliminate every factor except the language itself. Obi-Wan Kenobi, for example, also said, “You don’t need to see his identification,” but you don’t hear that a lot.

They asked a group of people who had not seen the movies to choose which quote in the pairs was most memorable. Two patterns emerged to identify the memorable choice: distinctiveness and generality.

Then the researchers programmed a computer with linguistic rules reflecting these concepts. A line will be less general if it contains third-person pronouns and definite articles (which refer to people, objects or events in the scene) and uses past tense (usually referring to something that happened previously in the story). Distinctive language can be identified by comparison with a database of news stories. The computer was able to choose the memorable quote an average of 64 percent of the time.

Later analysis also found subtle differences in sound and word choice: Memorable quotes use more sounds made in the front of the mouth, words with more syllables and fewer coordinating conjunctions.

In a further test, the researchers found that the same rules applied to popular advertising slogans.

Although teaching a computer how to write memorable dialogue is probably a long way off, applications might be developed to monitor the work of human writers and evaluate it in progress, Kleinberg suggested.

The researchers have set up a website where you can test your skill at identifying memorable movie quotes, and perhaps contribute some data to the research, at www.cs.cornell.edu/~cristian/memorability.html

Source: Science Daily

May 8, 2012

(Medical Xpress) — Having a fat head may not be a bad thing, according to new findings at The Johns Hopkins University. As reported in the February 9 issue of Neuron, Hopkins researchers have made a significant discovery as to how adding fat molecules to proteins can influence the brain circuitry controlling cognitive function, including learning and memory.

“When you learn something, you strengthen and inhibit certain transmissions and sculpt a particular circuit. Recall [or memory] is using that circuit again,” says Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at Johns Hopkins. His team’s latest finding describes for the first time how one protein chemically alters another in this circuit strengthening process and represents another step toward understanding a key part of how memories are made and maintained within the brain, something researchers believe could provide a pathway toward treating disorders like Alzheimer’s and schizophrenia.

In studying the molecular underpinnings of learning and memory, Huganir and his team have focused on one of several processes in which a molecule is tagged by another molecule of fat. Tagging sends the molecules to a particular destination within a cell. Specifically, the team has studied DHHC5, which is known to add a fat molecule to other proteins. Until now it was not known which proteins receive this tag.

The scientists suspected a target molecule would need to bind DHHC5, which would then transfer fat onto it. To determine what DHHC5 could bind, they used it as bait in a large pool of rat brain proteins to fish for those that stuck to DHHC5. Within that pool, DHHC5 bound four different proteins, researchers found. Using a computer program, they compared these with other proteins implicated in learning and memory. All four shared similarity with the brain protein known as GRIP1, mutations of which have been linked to disorders such as autism. The scientists then tested GRIP1 and DHHC5 directly and found that they bound each other as well. Next, they put GRIP1 into human kidney cells, either by itself or with DHHC5, and analyzed each group of cells to see what happened. They found that only the GRIP1 proteins that were added to cells with DHHC5 were tagged with fat. From this they concluded that DHHC5 does indeed tag GRIP1 with fat.

The researchers then wanted to know if this process happens in a brain. However, they needed a way to look into a living cell and be able to tell apart GRIP1 that had a fat tag and GRIP1 that didn’t. They designed two distinct GRIP1 proteins: one permanently tagged with fat, and another mutated so that it could never be tagged. They added color markers to both proteins so they could track them under a microscope, and then added one type or the other to living brain cells. The fat-tagged proteins seemed to form clusters extending to the cell’s edges in a pattern resembling that of cellular recycling-center proteins. The untagged proteins, in contrast, seemed to diffuse around the center of the cell. From this, the team concluded that DHHC5 tags proteins like GRIP1 with fat to send them to be recycled.

According to Huganir, protein recycling is critical for strengthening and maintaining memory circuits. Since GRIP1 is involved with recycling, it may be important in this critical aspect of memory formation. Huganir believes some day researchers could learn how to control this mechanism and reverse the disease process for disorders like Alzheimer’s and schizophrenia.

“Some day we may be able to inhibit or activate these molecules,” Huganir says. “These molecules are involved in mediating everything in the brain, all behaviors.”

Provided by Johns Hopkins University

Source: medicalxpress.com

ScienceDaily (May 7, 2012) — Badly controlled diabetes are known to affect the brain causing memory and learning problems and even increased incidence of dementia, although how this occurs is not clear. But now a study in mice with type 2 diabetes has discovered how diabetes affects a brain area called hippocampus causing memory loss, and also how caffeine can prevent this. 

Curiously, the neurodegeneration that Rodrigo Cunha  from the Centre for Neuroscience and Cell Biology of the University of Coimbra in Portugal see caused by diabetes is the same that occurs at the first stages of several neurodegenerative diseases, including Alzheimer’s and Parkinson’s, suggesting that caffeine (or drugs with similar mechanism) could help them too.

 Type 2 diabetes (which accounts for about 90%of all diabetic cases) is a full blown public health disaster – 285 million people affected worldwide (6.4% of the world population) with numbers expected to almost double by 2030. And this without counting pre-diabetic individuals. The problem is that the disease is triggered by obesity, sedentary lifestyle and bad eating habits (although there is also a genetic predisposition), all of which are increasingly widespread. 

Diabetes is caused by high levels of sugar in the blood, and in type 2 this occurs because the body becomes increasingly resistant to insulin –the hormone that allows the cells to take the sugar from the blood to use it as “fuel” – resulting in toxic high levels of sugar  in the blood that damage nerves and blood vessels and, with time, cause severe complications

 In the study out now in the journal PLoS , João Duarte, Rodrigo Cunha and colleagues take advantage of a new mouse model of diabetes type 2, which, like humans, develops the disease in adults as result of a high-fat diet, to look at one of the least understood complications of diabetes – the disease effect on the brain, more specifically, on memory. They also investigate a possible protective effect by caffeine as this psychostimulant has been suggested to prevent memory loss in a series of neurodegenerative diseases, maybe even in diabetes, although how this happens is not known. And when we consider that coffee is the world leading beverage right after water, with about 500 billion cups consumed annually, this, if true, needs to be better understood.

With that aim  the Portuguese researchers compared four groups of mice - diabetic or normal animals without or with caffeine (equivalent to 8 cups of coffee a day) in their water – to find that long-term consumption of caffeine not only diminished the weight gain and the high levels of blood sugar typical of diabetes, but also prevented the mice’s memory loss (diabetic animals had significantly poorer memory than normal ones). This confirmed that caffeine could, in fact, protect against diabetes as well as prevent memory impairment, probably by interfering with the neurodegeneration caused by toxic sugar levels.

To investigate this, next, the researchers looked at a brain region linked to memory and learning, which is often atrophied in diabetics, called hippocampus. And in fact, diabetic mice had abnormalities in this area showing synaptic degeneration (synapses are the structures at the end of each neuron used to communicate between neurons) and astrogliosis (an abnormal increase of the cells that surround neurons normally as result of the deathof nearby neurons). Both phenomena are known to affect memory and caffeine consumption  prevented the abnormalities.

But to be able to develop drugs based on caffeine’s protective effect, it was necessary to understand its molecular mechanisms. So next the researchers looked at the only brain molecules known to respond to caffeine – the adenosine receptors A1R and A2AR - in the hippocampus. And here, A2AR seemed to be the key for caffeine’s memory rescue since its density - which increases with noxious insults - was high in diabetic animals but normal in those treated with caffeine. This agrees with the previous studies that showed that A2AR inhibition protected against synaptic degeneration and memory dysfunction.

In conclusion, Duarte and Cunha’s work – using an animal model of diabetes type 2 that closely mimics the human form of the disease – suggests that diabetes affects memory by causing synaptic degeneration, astrogliosis and increased levels of A2AR. The study indicates as well that chronic consumption of caffeine can prevent the neurodegeneration and the memory impairment. And this not only in diabetes, since synaptic degeneration and astrogliosis are both part of a cascade of events common to several neurodegenerative diseases, suggesting that caffeine (or similar drugs) could help them too through the same mechanisms.

So does this means that we should drink eight cups of coffee a day to prevent memory loss in old age or diabetes? 

Not really as Rodrigo Cunha, the team leader explains: “Indeed, the dose of caffeine shown to be effective is just too excessive. All we can take from here is that a moderate consumption of caffeine should afford a moderate benefit, but still a benefit. Such experimental design is common in pre-clinical studies: in order to highlight a clear benefit, one dramatises the tested doses. But it’s an important first step. Our ultimate goal is the design of a drug more potent and selective (i.e. with less potential side effects) than caffeine itself; animal studies enable us to pinpoint the likely target of caffeine with protective benefits in type 2 diabetes. So now we will be testing chemical derivates of caffeine, which act as selective adenosine A2A receptor antagonists,to try to prevent diabetic encephalopathy. It might turn out to be a therapeutic breakthrough for this devastating disease”. 

And a breakthrough in a disease that is already affecting 6.4% of the population and growing can never come too soon.

Source: Science Daily

April 2, 2012

A team of University of Pittsburgh mathematicians is using computational models to better understand how the structure of neural variability relates to such functions as short-term memory and decision making. In a paper published online April 2 in Proceedings of the National Academy of Sciences (PNAS), the Pitt team examines how fluctuations in brain activity can impact the dynamics of cognitive tasks.

Previous recordings of neural activity during simple cognitive tasks show a tremendous amount of trial-to-trial variability. For example, when a person was instructed to hold the same stimulus in working, or short-term, memory during two separate trials, the brain cells involved in the task showed very different activity during the two trials.

"A big challenge in neuroscience is translating variability expressed at the cellular and brain-circuit level with that in cognitive behaviors," said Brent Doiron, assistant professor of mathematics in Pitt’s Kenneth P. Dietrich School of Arts and Sciences and the project’s principal investigator. "It’s a fact that short-term memory degrades over time. If you try to recall a stored memory, there likely will be errors, and these cognitive imperfections increase the longer that short-term memory is engaged."

Doiron explains that brain cells increase activity during short-term memory functions. But this activity randomly drifts over time as a result of stochastic (or chance) forces in the brain. This drifting is what Doiron’s team is trying to better understand.

"As mathematicians, what we’re really trying to do is relate the structure and dynamics of this stochastic variability of brain activity to the variability in cognitive performance," said Doiron. "Linking the variability at these two levels will give important clues about the neural mechanisms that support cognition."

Using a combination of statistical mechanics and nonlinear system theory, the Pitt team examined the responses of a model of a simplified memory network proposed to be operative in the prefrontal cortex. When sources of neural variability were distributed over the entire network, as opposed to only over subsections, the performance of the memory network was enhanced. This helped the Pitt team make the prediction published in PNAS, that brain wiring affects how neural networks contend with—and ultimately express—variability in memory and decision making.

Recently, experimental neurosciencists are getting a better understanding of how the brain is wired, and theories like those published in PNAS by Doiron’s group give a context for their findings within a cognitive framework. The Doiron group plans to apply the general principle of linking brain circuitry to neural variability in a variety of sensory, motor, and memory/decision-making frameworks.

Provided by University of Pittsburgh

Source: medicalxpress.com