SCIENTISTS REVEAL MOLECULAR SCULPTOR OF MEMORIES
ScienceDaily (Sep. 27, 2011) - Researchers working with adult mice have discovered that learning and memory were profoundly affected when they altered the amounts of a certain protein in specific parts of the mammals' brains.
The protein, called kibra, was linked in previous studies in humans to memory and protection against late-onset Alzheimer's disease. The new work in mice, reported in the Sept. 22 issue of Neuron, shows that kibra is an essential part of a complex of proteins that control the sculpting of brain circuitry, a process that encodes memory.
"There are populations of humans who are slightly smarter and have better memory recall than others, and these traits have been mapped to the gene that codes for the kibra protein" says Richard L. Huganir, Ph.D., professor and director of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine, and a Howard Hughes Medical Institute investigator. "Our studies in mice show that this same gene is involved in the operation of synapses, through which neurons communicate, and in brain plasticity, suggesting that's what its role might be in humans too."
In their lab, Huganir and neuroscience graduate student Lauren Makuch isolated kibra from mouse brain cells and confirmed by standard biochemical tests that it interacted with a neurotransmitter receptor in the brain known as the AMPA receptor.
They then determined that kibra regulated the delivery of AMPA receptors from inside the brain's nerve cells out to the synapses by first growing live brain cells from embryonic mice in a dish for two weeks and then genetically altering some of those cells to produce less kibra protein. Next, they placed the live neurons in an imaging chamber and recorded the activity of the AMPA receptors once a minute for 60 minutes. Results showed that AMPA receptors moved faster in the cells with less kibra than in control cells with normal amounts of the protein demonstrating that kibra regulates how receptors are delivered to the surface of brain cells.
The work affirms that the addition of AMPA receptors to synapses serves to strengthen connections in the brain, Huganir says, noting that most forms of learning involve the strengthening of some synapses and the weakening of others, a phenomenon known as plasticity, which is responsible for sculpting circuits in the brain that encode memory. Without kibra, this process doesn't function properly; as a result, learning and memory are compromised. Huganir hypothesizes that kibra specifically helps create a pool of receptors that is used to add receptors to synapses during learning.
Later in their study, using slices of brain from mice with or without kibra, postdoctoral fellow Lenora Volk recorded and measured electrical activity and synaptic plasticity in nerve cells, noting that mice lacking kibra showed less plasticity, a phenomenon that translates into a reduced ability to learn and recall new information, Makuch explains.
Finally, the Hopkins researchers conducted a series of behavioral studies using adult mice to compare the learning and memory of normal mice with those that made much less kibra protein. They used a well-established fear-conditioning task by placing the mice in a training chamber and exposing them to a tone and subsequent shock. After two days of training, the animals' rates of "freezing" in place -- a normal rodent response to fear -- were measured. Kibra-deficient mice took longer to learn to associate the tone with the shock than it did the others. On day three of the experiment, upon simply being placed back into the training chamber, the normal mice had a high rate of freezing, while the kibra-deficient mice had a very low rate, indicating impairments in contextual fear response and therefore, memory.
"Our work in the mammalian brain shows that kibra, required for normal brain function and associated with learning and memory, is important for regulating the trafficking of AMPA receptors," Huganir says. "In addition, as kibra has been associated with protection against early onset Alzheimer's disease, these studies may help define novel therapeutic targets for the treatment of age-related memory disorders."
HEART RISKS MORE IN OBESE PREGNANT LADIES CHILDREN
Researchers have uncovered evidence to show that piling on too many pounds in pregnancy may lead to future heart risks in the child.
The new research from the University of Bristol's Children of the 90s project (http://www.bristol.ac.uk/alspac/), shows that women who put on more weight during pregnancy than recommended by the 2009 Institute of Medicine's guidelines had children who at the age of nine:
- Were 1 kg heavier than children of mothers who gained the recommended amount
- Had larger waists by 2 cm
- Had more body fat by 1 kg
- Had higher systolic blood pressure by 1 mmHg
- Had higher levels of inflammatory markers by 15 per cent
- Had lower levels of (good) HDL cholesterol by 0.03 mmol/l
Antenatal records were used to collect detailed information about mothers' weight gain during pregnancy. Over 5,000 Children of the 90s youngsters were assessed at nine-years-old and blood samples were available for 3,457 children. Researchers studied the associations between pre-pregnancy weight and weight gain in pregnancy with cardiovascular disease risk factors in the children.
Professor Debbie Lawlor and her colleagues' research is published in the latest edition of Circulation: Journal of the American Heart Association.
She points out that information from the Children of the 90s research has been vital in this research as, at the time the women were pregnant, it was routine to regularly check the weight of pregnant women at every antenatal clinic. However, this practice was stopped in the mid-1990's so that the Children of the 90s study is a unique resource for studying the effects of weight gain in pregnancy.
"What the ideal weight gain is in pregnancy is a much debated question and at the moment we do not know the answer," cautions Professor Lawlor, who is the deputy director of the MRC's CAiTE Centre* at the University of Bristol.
This is because weight gain in pregnancy is complex and reflects not only how the baby is growing but also how much weight the mother has put on, how much amniotic fluid there is and how much the mother's blood volume has increased. Therefore the ideal weight gain in pregnancy should reflect what is best for both mother and child in both the short term (around the time of birth) and the long term.
Dr Abigail Fraser also from the CAiTE Centre and a co-author on the paper adds: "Our research also shows that perhaps even more important than the weight gained in pregnancy is how much a woman weighs before she gets pregnant.
"This supports initiatives aimed at maintaining a healthy weight in women of reproductive age."
SLEEP DISORDERS
Neuroscientists now believe sleep is not only crucial to brain development, but is also necessary to help consolidate the effects of waking experience - by converting memory into more permanent and/or enhanced forms.
Sleeping problems are almost always involved in mental disorders, including stress, depression, schizophrenia, Alzheimer's disease, stroke, as well as head injury. The symptoms are strongly influenced by the amount of sleep a person gets. Difficulties may arise from the drugs used to control symptoms of a disorder, or from changes in the brain regions and neurotransmitters that control sleep.
We will try to understand the subject under the following topics:
- Stress, Behavior and Sleep
- The Effects of Snoring
- How Sleep Benefits Brains
Stress, Behavior and Sleep
Many of us know what it is like to go without sleep and how it can affect our mood and stress level. Here you will find important information about why you may be losing sleep and intriguing studies about sleep deprivation. You may be surprised.
The Effects of Sleep Deprivation
Adequate sleep is crucial to proper brain function - no less so than air, water, and food - but stress can modify sleep-wakefulness cycles.
Any amount of sleep deprivation will diminish mental performance, cautions Mark Mahowald, a professor of neurology at the University of Minnesota Medical School. "One complete night of sleep deprivation is as impairing in simulated driving tests as a legally intoxicating blood-alcohol level."
At the American Diabetes Association's annual meeting, Eve Van Cauter, Ph.D., reported that people who regularly do not get enough sleep can become less sensitive to insulin. This increases their risk for diabetes and high blood pressure - both serious threats to the brain.
Previous work by Dr. Van Cauter, a professor of medicine at the University of Chicago, found that "metabolic and endocrine changes resulting from a significant sleep debt mimic many of the hallmarks of aging. We suspect that chronic sleep loss may not only hasten the onset but could also increase the severity of age-related ailments such as diabetes, hypertension, obesity, and memory loss."
Stress Hormones and Insomnia-Study
That stress can affect proper sleep seems obvious, but researchers at Pennsylvania State University College of Medicine have found another reason why middle-aged men may be losing sleep. It's not just because of what they worry about. Rather, it's due to "increased vulnerability of sleep to stress hormones," according to Dr. Alexandros N. Vgontzas.
As men age, it appears they become more sensitive to the stimulating effects of corticotropin-releasing hormone (CRH). When both young and middle-aged men were administered CRH, the older men remained awake longer and slept less deeply. (People who don't get enough of this "slow-wave" sleep may be more prone to depression.)
"The increased prevalence of insomnia in middle-age may, in fact, be the result of deteriorating sleep mechanisms associated with increased sensitivity to arousal-producing stress hormones, such as CRH and cortisol," Vgontzas and colleagues suggest.
In another study, the researchers compared patients with insomnia to those without sleep disturbances. They found that "insomniacs with the highest degree of sleep disturbance secreted the highest amount of cortisol, particularly in the evening and nighttime hours," suggesting that chronic insomnia is a disorder of sustained hyperarousal of the body's stress response system.
Stress and Sleep Patterns-Study
Why do some people lose sleep during periods of stress, while others seem to "sleep like a baby"? Research suggests that the difference may be explained by the ways people cope.
At Tel Aviv University, Dr. Avi Sadeh conducted a study of students. He found that those "who tended to focus on their emotions and anxiety during the high-stress period were more likely to shorten their sleep, while those who tended to ignore emotions and focus on tasks extended their sleep and shut themselves off from stress."
The researchers think that "stress may take the blame. During a routine week of studies, and again during a highly stressful month, sleep patterns of 36 students (aged 22 to 32) were documented. Sleep quality improved or remained the same for students who directed their focus away from their emotions, but diminished for those who fretted and brooded as a way to cope with stress.
Almost titling his paper, "If you can't cope with it, sleep on it," Sadeh said "sometimes sleep can help you regulate your nervousness and offer you an escape from stress, particularly when there's nothing you can do about it."
Children's Sleep Patterns Related to Behavior-Study
A Northwestern University study of 500 preschoolers found that those who slept less than 10 hours in a 24-hour period (including daytime naps) were 25% more likely to misbehave. They were consistently at greatest risk for "acting out" behavioral problems, such as aggression and oppositional or noncompliant behavior.
Research shows that sleep disturbances in children are not only associated with medical problems (allergies, ear infections, hearing problems), but also with psychiatric and social issues. Children who were aggressive, anxious, or depressed had more trouble falling and staying asleep. Although sleep problems usually decline as children get older, these early patterns are the best indicator of future sleep troubles.
OSTEOARTHRITIS PATIENTS & EXERCISES
Adherence to Recommended Exercise Improves Physical Function, Reduces Pain for Osteoarthritis Patients.
Patients with osteoarthritis (OA) of the knee or hip who adhere to the recommended home physical therapy exercises and physically active lifestyle experience more improvement in pain, physical function, and self-perceived effect according to a study from researchers in the Netherlands. Research also shows that maintenance of exercise behavior and physically active lifestyle after discharge of physical therapy improves the long-term effectiveness of exercise therapy in patients with knee or hip OA.
Details of the study are available online and will publish in the August print issue of Arthritis Care & Research, a journal of the American College of Rheumatology.
Individuals with OA of the hip or knee experience pain, reduced muscle strength, decreased range of joint motion, and joint instability. According to the World Health Organization (WHO) OA is one of the ten most disabling diseases in developed countries. Further WHO estimates state that 80% of those with OA have limitations in movement, and 25% cannot perform major daily life activities. Often OA patients are referred to physical therapy in order to reduce impairments and improve overall physical function to meet demands of daily living. Although exercise therapy has beneficial short-term effects, earlier research has shown that after discharge of exercise therapy the positive treatment effects decline over time and finally disappear in the long-term.
The Dutch research team conducted an observational follow-up study on 150 patients with OA of the hip and/or knee who were receiving exercise therapy. The study subjects were followed for 60 months to assess adherence to self-directed exercise (during and after prescribed physical therapy treatment period) on patient outcomes of pain, physical function, and self-perceived effect. Three forms of adherence, which is defined as the subject's behavior that corresponds to agreed recommendations by his or her physical therapist, were measured-adherence to home exercises, home activities, and increased physical activity. Researchers used a self-report questionnaire to measure participants' adherence to home exercise (e.g. muscle strengthening exercises) and activity (e.g. walking or cycling). Assessment of adherence started at baseline, and then took place again at 3, 15, and 60 months.
Patient outcomes of pain and physical function were measured using the Western
Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score. The WOMAC scale ranges from best to worst, meaning lower scores represent less pain and improved physical function. Participants' physical performance was measured by the time (in seconds) it took to walk the distance of 5 meters with improvement in performance noted by a reduction in time to complete the walk.
Results show at the 3-month follow-up 57.8% of study subjects adhered to the recommended exercises and 53.8% to recommended activities. Adherence to exercise was significantly associated with a decrease in pain (1.0 points on a scale from 0 to 20), and improvements in self-reported physical function (2.3 points on a scale from 0 to 68) and physical performance (-0.29 seconds compared with the base-line time of 4.8 seconds to walk 5 meters (16 feet)). "Better adherence to home exercises and being more physically active improves the long-term effectiveness of exercise therapy in patients with OA of the hip and/or knee," said lead study author, Martijn Pisters, M.Sc., PT.
A higher level of moderate or vigorous intensity physical activity was significantly associated with a decrease in pain, physical function and physical performance, as well as a positive self-perceived effect. The authors found that one hour per week more of physical activity at a moderate level resulted in an improvement in self-reported physical function of -0.24 on a scale from 0 to 68. During the physical therapy treatment period, the patients' physical activity increased by 1.5 hours of moderate or vigorous intensity physical activity per week. After the treatment period, physical activity declined by 0.5 and 1.3 hours respectively at the 15- and 60-month follow-up.
Additionally, researchers noted a decline in exercise adherence upon completion of physical therapy with only 44.1% of patients and 30.1% still exercising at the 15- and 60-month follow-up, respectively. Similarly, adherence to home activities decreased at the 15 - and 60-month follow-up with only with 29.5% and 36%, respectively, of study subjects being adherent. "Future research should focus on how exercise behavior can be stimulated and maintained in the long term to improve outcomes for patients with OA," concluded Mr. Pisters.
The above story is reprinted (with editorial adaptations by ScienceDaily staff) from materials provided by Wiley - Blackwell, via AlphaGalileo.
Martijn F Pisters, Cindy Veenhof, François G Schellevis, Jos WR Twisk, Joost Dekker, Dinny H De Bakker. Exercise adherence improves long-term patient outcome in patients with osteoarthritis of the hip and/or knee.
