Posts tagged science

ScienceDaily (July 18, 2012) — Researchers from the University of Medicine and Dentistry of New Jersey (UMDNJ), collaborating with scientists from Northwestern University in Illinois, have provided direct experimental evidence that diabetes is linked to the onset of Alzheimer’s disease. The study, published online this week in the Journal of Alzheimer’s Disease, used an experimental model that shows potential as an important new tool for investigations of Alzheimer’s disease and of drugs being developed to treat Alzheimer’s.

UMDNJ researchers Peter Frederikse, PhD, and Chinnaswamy Kasinathan, PhD, collaborated with William Klein, PhD, at Northwestern University, to build on prior studies from the Klein lab and others that indicated close links between Alzheimer’s disease and diabetes. Working with Claudine Bitel and Rajesh Kaswala, students at UMDNJ, the researchers tested whether untreated diabetes would provide a physiological model of Alzheimer neuropathology.

"The results were striking," Frederikse said. "Because we used diabetes as an instigator of the disease, our study shows — for the first time directly — the link between Alzheimer’s and diabetes."

The researchers found substantial increases in amyloid beta peptide pathology — a hallmark of Alzheimer’s disease — in the brain cortex and hippocampus concurrent with diabetes. They also found significant amyloid beta pathology in the retina and by contrast, when diabetes is not present, no observable pathology was detected in either the brain or the retina.

"Second, our study examined the retina, which is considered an extension of the brain, and is more accessible for diagnostic exams," Frederikse added. "Our findings indicate that scientists may be able to follow the onset and progression of Alzheimer’s disease through retinal examination, which could provide a long sought after early-warning sign of the disease."

This experimental model replicated spontaneous formation of amyloid beta “oligomer” assemblies in brain and retina which may help to explain one of the most widely recognized symptoms of Alzheimer’s. “This is exciting,” Klein said. “Oligomers are the neurotoxins now regarded as causing Alzheimer’s disease memory loss. What could cause them to appear and buildup in late-onset Alzheimer’s disease has been a mystery, so these new findings with diabetes represent an important step.”

Previous research indicated that insulin plays an important role in the formation of memories. Once attached to neurons, oligomers cause insulin receptors to be eliminated from the surface membranes, contributing to insulin resistance in the brain. This launches a vicious cycle in which diabetes induces oligomer accumulation which makes neurons even more insulin resistant.

"In light of the near epidemic increases in Alzheimer’s disease and diabetes today, developing a physiological model of Alzheimer neuropathology has been an important goal," Kasinathan added. "It allows us to identify a potential biomarker for Alzheimer’s disease and may also make important contributions to Alzheimer drug testing and development."

Source: Science Daily

7/18/2012

Metabolic syndrome, a term used to describe a combination of risk factors that often lead to heart disease and type 2 diabetes, seems to be linked to lower blood flow to the brain, according to research by the University of Wisconsin School of Medicine and Public Health.

Dr. Barbara Bendlin, researcher for the Wisconsin Alzheimer’s Disease Research Center and an assistant professor of medicine (geriatrics) at the UW School of Medicine and Public Health, said study participants with multiple risk factors connected to metabolic syndrome, including abdominal obesity, high blood pressure, high blood sugar and high cholesterol averaged 15 percent less blood flow to the brain than those in a control group, according to results of brain scans to measure cerebral blood flow.

"We thought the cerebral blood flow measurements of the metabolic syndrome group would be lower, but it was striking how much lower it was," said Bendlin.

Although lower blood flow could result in an eventual reduction in memory skills, Bendlin said it is not known if people with metabolic syndrome will get Alzheimer’s disease.

"Having metabolic syndrome at middle age does have an effect on the brain, and there is some suggestion that if you have lower blood flow, certain types of memory functions are reduced," she said. "The key will be to follow these people over time, because we want to know if lower blood flow will lead to a gradual loss of memory and cognitive skills. But it’s too early to say if these people will develop Alzheimer’s."

The study, presented today at the Alzheimer’s Association International Conference in Vancouver, British Columbia, involved 71 middle-aged people recruited from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). Of this group, 29 met the criteria for metabolic syndrome and 42 did not.

Bendlin said the next steps will be to conduct additional brain scans on people with metabolic syndrome to get more specifics on why they have reduced cerebral blood flow.

"By comparing people with metabolic syndrome with those who don’t, we don’t know which of the risk factors are worst," she said. "Is having a high blood-glucose level worse than having high blood pressure or is it different than having abdominal obesity? All of these risk factors have been linked to increased risk for dementia, but they are clustered together. If we knew which ones were the worst, those would be the ones to target with specific treatments."

Source: Bio-Medicine

July 18, 2012

Drugs used to treat Attention Deficit Hyperactivity Disorder (ADHD) do not appear to have long-term effects on the brain, according to new animal research from Wake Forest Baptist Medical Center.

As many as five to seven percent of elementary school children are diagnosed with ADHD, a behavioral disorder that causes problems with inattentiveness, over-activity, impulsivity, or a combination of these traits. Many of these children are treated with psychostimulant drugs, and while doctors and scientists know a lot about how these drugs work and their effectiveness, little is known about their long-term effects.

Linda Porrino, Ph.D., professor and chair of the Department of Physiology and Pharmacology, along with fellow professor Michael A. Nader, Ph.D., both of Wake Forest Baptist, and colleagues conducted an animal study to determine what the long-lasting effects may be. Their findings were surprising, said Porrino. “We know that the drugs used to treat ADHD are very effective, but there have always been concerns about the long-lasting effects of these drugs,” Porrino said.

"We didn’t know whether taking these drugs over a long period could harm brain development in some way or possibly lead to abuse of drugs later in adolescence."

Findings from the Wake Forest Baptist research are published online this month in the journal Neuropsychopharmacology.

The researchers studied 16 juvenile non-human primates, whose ages were equivalent to 6-to 10-year-old humans. Eight animals were in the control group that did not receive any drug treatment and the other eight were treated with a therapeutic-level dose of an extended-release form of Ritalin, or methylphenidate (MPH), for over a year, which is equivalent to about four years in children. Imaging of the animals’ brains, both before and after the study, was conducted on both groups to measure brain chemistry and structure. The researchers also looked at developmental milestones to address concerns that ADHD drugs adversely affect physical growth.

Once the MPH treatment and imaging studies were concluded, the animals were given the opportunity to self administer cocaine over several months. Nader measured their propensity to acquire the drug and looked at how rapidly and in what amounts, to provide an index of vulnerability to substance abuse in adolescence. As reported in the research paper, they found no differences between groups – monkeys treated with Ritalin during adolescence were not more vulnerable to later drug use than the control animals.

"After one year of drug therapy, we found no long-lasting effects on the neurochemistry of the brain, no changes in the structure of the developing brain. There was also no increase in the susceptibility for drug abuse later in adolescence," Porrino said. "We were very careful to give the drugs in the same doses that would be given to children. That’s one of the great advantages of our study is that it’s directly translatable to children."

Porrino said non-human primates provide exceptional models for developmental research because they undergo relatively long childhood and adolescent periods marked by hormonal and physiological maturation much like humans.

"Our study showed that long-term therapeutic use of drugs to treat ADHD does not cause long-term negative effects on the developing brain, and importantly, it doesn’t put children at risk for substance abuse later in adolescence," she said.

One of the exciting things about this research, Porrino said, is that a “sister” study was conducted simultaneously at John Hopkins with slightly older aged animals and different drugs and their findings were similar. “We feel very confident of the results because we have replicated each other’s studies within the same time frame and gotten similar results,” she said. “We think that’s pretty powerful and reassuring.”

Provided by Wake Forest University Baptist Medical Center

Source: medicalxpress.com

July 18, 2012

A new guideline released by the American Academy of Neurology recommends several treatments for people with Huntington’s disease who experience chorea—jerky, random, uncontrollable movements that can make everyday activities challenging. The guideline is published in the July 18, 2012, online issue of Neurology.

"Chorea can be disabling, worsen weight loss and increase the risk of falling," said guideline lead author Melissa Armstrong, MD, MSc, with the University of Maryland Department of Neurology and a member of the American Academy of Neurology.

Huntington’s disease is a complex disease with physical, cognitive and behavioral symptoms. The new guideline addresses only one aspect of the disease that may require treatment.

The guideline found that the drugs tetrabenazine (TBZ), riluzole and amantadine can be helpful and the drug nabilone may also be considered to treat chorea. The medications riluzole, amantadine and nabilone are not often prescribed for Huntington’s disease.

"People with Huntington’s disease who have chorea should discuss with their doctors whether treating chorea is a priority. Huntington’s disease is complex with a wide range of sometimes severe symptoms and treating other symptoms may be a higher priority than treating chorea," said Armstrong.

Armstrong adds that it is important for patients to understand that their doctors may try drugs not recommended in this guideline to treat chorea. More research is needed to know if drugs such as those used for psychosis are effective; however, doctors may prescribe them on the basis of past clinical experience.

Provided by American Academy of Neurology

Source: medicalxpress.com

July 18, 2012

Sleep deprivation in the first few hours after exposure to a significantly stressful threat actually reduces the risk of Post-Traumatic Stress Disorder (PTSD), according to a study by researchers from Ben-Gurion University of the Negev (BGU) and Tel Aviv University.

The new study was published in the international scientific journal, Neuropsychopharmacology. It revealed in a series of experiments that sleep deprivation of approximately six hours immediately after exposure to a traumatic event reduces the development of post trauma-like behavioral responses. As a result, sleep deprivation the first hours after stress exposure might represent a simple, yet effective, intervention for PTSD.

The research was conducted by Prof. Hagit Cohen, director of the Anxiety and Stress Research Unit at BGU’s Faculty of Health Sciences, in collaboration with Prof. Joseph Zohar of Tel Aviv University.

Approximately 20 percent of people exposed to a severe traumatic event, such as a car or work accident, terrorist attack or war, cannot normally carry on their lives. These people retain the memory of the event for many years. It causes considerable difficulties in the person’s functioning in daily life and, in extreme cases, may render the individual completely dysfunctional.

"Often those close to someone exposed to a traumatic event, including medical teams, seek to relieve the distress and assume that it would be best if they could rest and "sleep on it," says Prof. Cohen. "Since memory is a significant component in the development of post-traumatic symptoms, we decided to examine the various effects of sleep deprivation immediately after exposure to trauma."

In the experiments, rats that underwent sleep deprivation after exposure to trauma (predator scent stress exposure), later did not exhibit behavior indicating memory of the event, while a control group of rats that was allowed to sleep after the stress exposure did remember, as shown by their post trauma-like behavior.

"As is the case for human populations exposed to severe stress, 15 to 20 percent of the animals develop long-term disruptions in their behavior," says Cohen. "Our research method for this study is, we believe, a breakthrough in biomedical research."

A pilot study in humans is currently being planned. The studies were funded by a Israel Academy of Science and Humanities grant and the Israel Ministry of Health.

Provided by American Associates, Ben-Gurion University of the Negev

Source: medicalxpress.com

July 18, 2012

(Phys.org) — New research at the Hebrew University of Jerusalem sheds light on pluripotency—the ability of embryonic stem cells to renew themselves indefinitely and to differentiate into all types of mature cells. Solving this problem, which is a major challenge in modern biology, could expedite the use of embryonic stem cells in cell therapy and regenerative medicine. If scientists can replicate the mechanisms that make pluripotency possible, they could create cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer’s, Parkinson’s, diabetes and other degenerative diseases.

To shed light on these processes, researchers in the lab of Dr. Eran Meshorer, in the Department of Genetics at the Hebrew University’s Alexander Silberman Institute of Life Sciences, are combining molecular, microscopic and genomic approaches. Meshorer’s team is focusing on epigenetic pathways—which cause biological changes without a corresponding change in the DNA sequence—that are specific to embryonic stem cells.

The molecular basis for epigenetic mechanisms is chromatin, which is comprised of a cell’s DNA and structural and regulatory proteins. In groundbreaking research performed by Shai Melcer, a PhD student in the Meshorer lab, the mechanisms which support an “open” chromatin conformation in embryonic stem cells were examined. The researchers found that chromatin is less condensed in embryonic stem cells, allowing them the flexibility or “functional plasticity” to turn into any kind of cell.

A distinct pattern of chemical modifications of chromatin structural proteins (referred to as the acetylation and methylation of histones) enables a looser chromatin configuration in embryonic stem cells. During the early stages of differentiation, this pattern changes to facilitate chromatin compaction.

But even more interestingly, the authors found that a nuclear lamina protein, lamin A, is also a part of the secret. In all differentiated cell types, lamin A binds compacted domains of chromatin and anchors them to the cell’s nuclear envelope. Lamin A is absent from embryonic stem cells and this may enable the freer, more dynamic chromatin state in the cell nucleus. The authors believe that chromatin plasticity is tantamount to functional plasticity since chromatin is made up of DNA that includes all genes and codes for all proteins in any living cell. Understanding the mechanisms that regulate chromatin function will enable intelligent manipulations of embryonic stem cells in the future.

"If we can apply this new understanding about the mechanisms that give embryonic stem cells their plasticity, then we can increase or decrease the dynamics of the proteins that bind DNA and thereby increase or decrease the cells’ differentiation potential," concludes Dr. Meshorer. “This could expedite the use of embryonic stem cells in cell therapy and regenerative medicine, by enabling the creation of cells in the laboratory which could be implanted in humans to cure diseases characterized by cell death, such as Alzheimer’s, Parkinson’s, diabetes and other degenerative diseases.”

Source: PHYS.ORG