ScienceDaily (July 31, 2012) — New research demonstrates that blocking the delta opioid receptor in mice created resistance to weight gain and stimulated gene expression promoting non-shivering thermogenesis.

Imagine eating all of the sugar and fat that you want without gaining a pound. Thanks to new research published in The FASEB Journal, the day may come when this is not too far from reality. That’s because researchers from the United States and Europe have found that blocking one of three opioid receptors in your body could turn your penchant for sweets and fried treats into a weight loss strategy that actually works. By blocking the delta opioid receptor, or DOR, mice reduced their body weight despite being fed a diet high in fat and sugar. The scientists believe that the deletion of the DOR gene in mice stimulated the expression of other genes in brown adipose tissue that promoted thermogenesis.

"Our study provided further evidence that opioid receptors can control the metabolic response to diets high in fat and sugar, and raise the possibility that these gene products (or their respective pathways) can be targeted specifically to treat excess weight and obesity," said Traci A. Czyzyk, Ph.D., a researcher involved in the work from the Department of Physiology at the Mayo Clinic in Scottsdale, Arizona.

Scientists studied mice lacking the delta opioid receptor (DOR KO) and wild type (WT) control mice who were fed an energy dense diet (HED), high in fat and sugar, for three months. They found that DOR KO mice had a lean phenotype specifically when they were fed the HED. While WT mice gained significant weight and fat mass on this diet, DOR KO mice remained lean even though they consumed more food. Researchers then sought to determine how DOR might regulate energy balance and found that DOR KO mice were able to maintain their energy expenditure levels, in part, due to an increase in non-shivering thermogenesis. This was evidenced by an increase in thermogenesis-promoting genes in brown adipose tissue, an increase in body surface temperature near major brown adipose tissue depots, and the ability of DOR KO mice to maintain higher core body temperatures in response to being in a cold environment.

"Don’t reach for the ice cream and doughnuts just yet," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal. “We don’t know how all this works in humans, and of course, a diet of junk food causes other health problems. This exciting research identifies genes that activate brown adipose tissue to increase our burning of calories from any source. It may lead to a safe diet pill in the future.”

Source: Science Daily

July 31, 2012

Wayne State University School of Medicine researchers, working with colleagues in Canada, have found that one or more substances produced by a type of immune cell in people with multiple sclerosis (MS) may play a role in the disease’s progression. The finding could lead to new targeted therapies for MS treatment.

B cells, said Robert Lisak, M.D., professor of neurology at Wayne State and lead author of the study, are a subset of lymphocytes (a type of circulating white blood cell) that mature to become plasma cells and produce immunoglobulins, proteins that serve as antibodies. The B cells appear to have other functions, including helping to regulate other lymphocytes, particularly T cells, and helping maintain normal immune function when healthy.

In patients with MS, the B cells appear to attack the brain and spinal cord, possibly because there are substances produced in the nervous system and the meninges — the covering of the brain and spinal cord — that attract them. Once within the meninges or central nervous system, Lisak said, the activated B cells secrete one or more substances that do not seem to be immunoglobulins but that damage oligodendrocytes, the cells that produce a protective substance called myelin.

The B cells appear to be more active in patients with MS, which may explain why they produce these toxic substances and, in part, why they are attracted to the meninges and the nervous system.

The brain, for the most part, can be divided into gray and white areas. Neurons are located in the gray area, and the white parts are where neurons send their axons — similar to electrical cables carrying messages — to communicate with other neurons and bring messages from the brain to the muscles. The white parts of the brain are white because oligodendrocytes make myelin, a cholesterol-rich membrane that coats the axons. The myelin’s function is to insulate the axons, akin to the plastic coating on an electrical cable. In addition, the myelin speeds communication along axons and makes that communication more reliable. When the myelin coating is attacked and degraded, impulses — messages from the brain to other parts of the body — can “leak” and be derailed from their target. Oligodendrocytes also seem to engage in other activities important to nerve cells and their axons. 

The researchers took B cells from the blood of seven patients with relapsing-remitting MS and from four healthy patients. They grew the cells in a medium, and after removing the cells from the culture collected material produced by the cells. After adding the material produced by the B cells, including the cells that produce myelin, to the brain cells of animal models, the scientists found significantly more oligodendrocytes from the MS group died when compared to material produced by the B cells from the healthy control group. The team also found differences in other brain cells that interact with oligodendrocytes in the brain.

"We think this is a very significant finding, particularly for the damage to the cerebral cortex seen in patients with MS, because those areas seem to be damaged by material spreading into the brain from the meninges, which are rich in B cells adjacent to the areas of brain damage," Lisak said.

The team is now applying for grants from several sources to conduct further studies to identify the toxic factor or factors produced by B cells responsible for killing oligodendrocytes. Identification of the substance could lead to new therapeutic methods that could switch off the oligodendrocyte-killing capabilities of B cells, which, in turn, would help protect myelin from attacks.

Provided by Wayne State University

Source: medicalxpress.com

July 31, 2012

(HealthDay) — For patients with dementia with Lewy bodies (DLB), treatment with 5 or 10 mg/day donepezil is associated with significant cognitive, behavioral, and global function improvements, according to research published in the July issue of the Annals of Neurology.

Etsuro Mori, M.D., Ph.D., of the Tohoku University Graduate School of Medicine in Sendai, Japan, and colleagues conducted a randomized, double-blind, placebo-controlled trial involving 140 patients with DLB who received either placebo or 3, 5, or 10 mg of donepezil hydrochloride per day for 12 weeks (35, 35, 33, and 37 patients, respectively). Cognitive function was measured using the Mini-Mental State Examination (MMSE); behavioral changes were measured using the Neuropsychiatric Inventory; global function was evaluated using the Clinician’s Interview-Based Impression of Change-plus Caregiver Input (CIBIC-plus); and caregiver burden was also assessed.

The researchers found that, compared with placebo treatment, the MMSE scores were significantly better with donepezil 5 mg (mean difference, 3.8) and 10 mg (mean difference, 2.4), but the 3 mg/day dose was not significantly better than placebo (P = 0.017). Donepezil at doses of 3, 5, and 10 mg/day correlated with significant improvements versus placebo on CIBIC-plus. Both the 5 and 10 mg doses of donepezil resulted in significant improvements in behavioral measures. Caregiver burden also improved, but only with the 10 mg/day dose. The safety results were similar among the groups and were consistent with the known profile.

"Donepezil at 5 and 10 mg/day produces significant cognitive, behavioral, and global improvements that last at least 12 weeks in DLB patients, reducing caregiver burden at the highest dose," the authors write. Several authors disclosed financial ties to pharmaceutical companies, including Eisai Co., which funded the study and manufactures donepezil.

Source: medicalxpress.com

Jul 31, 2012 by Laura Bailey

Concussions and even lesser head impacts may speed up the brain’s natural aging process by causing signaling pathways in the brain to break down more quickly than they would in someone who has never suffered a brain injury or concussion.

The photos compare images of two brains, one with and without head injury. The red areas indicates electrical activity in response to the task researchers asked study participants to perform, and non-injured brains show more red, thus more electrical activity during the task. Image courtesy of Steven Broglio

Researchers from the University of Michigan School of Kinesiology and the U-M Health System looked at college students with and without a history of concussion and found changes in gait, balance and in the brain’s electrical activity, specifically attention and impulse control, said Steven Broglio, assistant professor of kinesiology and director of the Neurotrauma Research Laboratory.

The declines were present in the brain injury group up to six years after injury, though the differences between the study groups were very subtle, and outwardly all of the participants looked and acted the same.

Broglio, who is also affiliated with Michigan NeuroSport, stressed that the studies lay out a hypothesis where concussions and head impacts accelerate the brain’s natural aging process.

The study, “Cognitive decline and aging: The role of concussive and subconcussive impacts,” appears in the July issue of journal Exercise and Sport Sciences Reviews.

"The last thing we want is for people to panic. Just because you’ve had a concussion does not mean your brain will age more quickly or you’ll get Alzheimer’s," Broglio said. "We are only proposing how being hit in the head may lead to these other conditions, but we don’t know how it all goes together just yet."

Broglio stressed that other factors, such as lifestyle choices, smoking, alcohol consumption, physical exercise, family history and whether or not you “exercise” your brain also impact the brain’s aging process. Concussion may only be one small factor.

To begin to understand how concussions might impact brain activity and its signaling pathways, researchers asked the participants to perform certain tasks in front of a computer, and took images of their brains. The brains of the nonconcussed group showed a greater area of electrical activation than the participants with a history of brain injury.

The signaling pathways in our brains are analogous to a five-lane highway. On a new highway, traffic runs smoothly and quickly as all lanes are in top shape. However, during normal aging, the asphalt deteriorates and lanes might become bumpy or even unusable. Traffic slows.

Similarly, our brains start with all pathways clear to transfer electrical signals rapidly. As we age, the brain’s pathways break down and can’t transfer the information as quickly. Concussive and other impacts to the head may result in a ‘pothole’ on the brain’s highway, causing varying degrees of damage and speeding the pathway’s natural deterioration.

"What we don’t know is if you had a single concussion in high school, does that mean you will get dementia at age 50?" Broglio said. "Clinically, we don’t see that. What we think is it will be a dose response.

"So, if you played soccer and sustained some head impacts and maybe one concussion, then you may have a little risk. If you went on and played in college and took more head balls and sustained two more concussions, you’re probably at a little bigger risk. Then if you play professionally for a few years, and take more hits to the head, you increase the risk even more. We believe it’s a cumulative effect."

In the next phase of study, researchers will look at people in their 20s, 40s and 60s who did and did not sustain concussions during high school sports. They hope to learn if there is an increasing effect of concussion as the study subjects age. If interested in participating in the study, email neurotraumalab.umich@gmail.com.

Researchers from the departments of Physical Medicine and Rehabilitation, and Neurology, and the Michigan Alzheimer’s Disease Center also participated in the study.

Source: University of Michigan

July 31, 2012

The presence of specific autoantibodies of the immune system is associated with blood vessel damage in the brain. These findings were made by Marion Bimmler, a graduate engineer of medical laboratory diagnostics at the Max Delbrück Center for Molecular Medicine Berlin-Buch and Dr. Peter Karczewski of the biotech company E.R.D.E.-AAK-Diagnostik GmbH in studies on a rat model. The researchers’ results suggest that autoimmune mechanisms play a significant role in the pathogenesis and progression of Alzheimer’s and vascular dementia.

(MR Angiography/Copyright: MDC)

Antibodies are the defense molecules of the body’s immune system against foreign invaders. If the antibodies cease to distinguish between “foreign” and “self”, they attack the cells of the own body, and are thus referred to as autoantibodies. These can trigger autoimmune diseases. Using MR angiography and other methods, Marion Bimmler and her colleagues have now shown that the autoantibodies bind to specific surface proteins (alpha1 andrenergic receptors) of vascular cells and thereby damage the blood vessels of the brain. The reason: The autoantibodies generate a continual stimulation of the receptor and at the same time trigger an increase in intracellular calcium ion levels. As a result, the blood vessel walls thicken, and blood flow to the brain is disturbed.

First Encouraging Results after Removal of Autoantibodies by Immunoadsorption

In earlier studies, Marion Bimmler and her research team examined blood samples of patients with Alzheimer’s or vascular dementia and showed that half of them had comparable autoantibodies. A first clinical trial together with Charité – Universitätsmedizin Berlin is currently ongoing with a collective of patients with Alzheimer’s or vascular dementia. The patients were divided into two groups – a small group whose autoantibodies were removed from the blood via immunoadsorption and a control group that did not receive this treatment. Until now, over an observation period of 6 and subsequently 12 months, the patient group who had undergone immunoadsorption improved in their memory performance and in their ability to cope with their everyday lives. In contrast, the condition of the patients who did not receive immunoadsorption treatment and continued to have autoantibodies in their blood deteriorated dramatically. Now the researchers are planning further clinical trials with larger numbers of patients.

Provided by Helmholtz Association of German Research Centres

Source: medicalxpress.com

Tuesday, July 31, 2012

TAU researchers develop bioactive coating to “camouflage” neutral electrodes

Brain-computer interfaces are at the cutting edge for treatment of neurological and psychological disorder, including Parkinson’s, epilepsy, and depression. Among the most promising advance is deep brain stimulation (DBS) — a method in which a silicon chip implanted under the skin ejects high frequency currents that are transferred to the brain through implanted electrodes that transmit and receive the signals. These technologies require a seamless interaction between the brain and the hardware.

But there’s a catch. Identified as foreign bodies by the immune system, the brain attacks the electrodes and forms a barrier to the brain tissue, making it impossible for the electrodes to communicate with brain activity. So while the initial implantation can diminish symptoms, after a few short years or even months, the efficacy of this therapy begins to wane.

Now Aryeh Taub of Tel Aviv University's School of Psychological Sciences, along with Prof. Matti Mintz, Roni Hogri and Ari Magal of TAU’s School of Psychological Sciences and Prof. Yosi Shacham-Diamand of TAU’s School of Electrical Engineering, has developed a bioactive coating which not only “camouflages” the electrodes in the brain tissue, but actively suppresses the brain’s immune response. By using a protein called an “interleukin (IL)-1 receptor antagonist” to coat the electrodes, the multi-disciplinary team of researchers has found a potential resolution to turn a method for short-term relief into a long-term solution. This development was reported in the Journal of Biomedical Materials Research.

Limiting the immune response

To overcome the creation of the barrier between the tissue and the electrode, the researchers sought to develop a method for placing the electrode in the brain tissue while hiding the electrode from the brain’s immune defenses. Previous research groups have coated the electrodes with various proteins, says Taub, but the TAU team decided to take a different approach by using a protein that is active within the brain itself, thereby suppressing the immune reaction against the electrodes.

In the brain, the IL-1 receptor antagonist is crucial for maintaining physical stability by localizing brain damage, Taub explains. For example, if a person is hit on the head, this protein works to create scarring in specific areas instead of allowing global brain scarring. In other words, it stops the immune system from overreacting. The team’s coating, the first to be developed from this particular protein, not only integrates the electrodes into the brain tissue, but allows them to contribute to normal brain functioning.

In pre-clinical studies with animal models, the researchers found that their coated electrodes perform better than both non-coated and “naïve protein”-coated electrodes that had previously been examined. Measuring the number of damaged cells at the site of implantation, researchers found no apparent difference between the site of electrode implantation and healthy brain tissue elsewhere, Taub says. In addition, evidence suggests that the coated electrodes will be able to function for long periods of time, providing a more stable and long-term treatment option.

Restoring brain function

Approximately 30,000 people worldwide are currently using deep brain stimulation (DBS) to treat neurological or psychological conditions. And DBS is only the beginning. Taub believes that, in the future, an interface with the ability to restore behavioral or motor function lost due to tissue damage is achievable — especially with the help of their new electrode coating.

"We duplicate the function of brain tissue onto a silicon chip and transfer it back to the brain," Taub says, explaining that the electrodes will pick up brain waves and transfer these directly to the chip. "The chip then does the computation that would have been done in the damaged tissue, and feeds the information back into the brain — prompting functions that would have otherwise gotten lost."

Source: Tel Aviv University