Alcoholism Found to Prevent Anxiety Through 'Remodeling' of Brain DNA

New studies found at the University of Illinois in Chicago, have found that the acute consumption of alcohol can reshape the DNA scaffolding that supports and controls the expression of genes in the brain which can lead to withdrawal symptoms, therefore making it difficult for alcoholics to cut back on alcohol.

"Epigenetic" changes are changes in DNA which can occur without any changes in inheritance or coded sequence, they are considered minor chemical modifications of chromatins - dense bundles of DNA and proteins called histones.

"This is the first time anyone has looked for epigenetic changes related to chromatin remodeling in the brain during alcohol addiction," said Dr Subhash C. Pandey, professor and director of neuroscience alcoholism research at the UIC College of Medicine.

Chemical modification of histones can affect and change the way DNA and histones are wound up together. Histone acetyltransferases (HATs) are enzymes that add acetyl groups to histones and loosen the packaging, promoting gene expression. On the other hand the are histone deacetylases (HDACs) which do the opposite by removing acetyl groups, causing them to wrap with DNA more tightly, therefore decreasing gene expression.

The researchers at UIC, Pandey and his colleagues found that acute exposure to alcohol can decrease HDAC activity, therefore increase the acetylation histones, leading to an increase in neuropeptides Y. In studies on an animal model researchers found that NPY (neuropeptides Y) can modulate anxiety.

During these studies anxiety-like behaviours during withdrawal in animals with chronic alcohol exposure had an increase in HDAC activity, decrease in histones acetylation and NPY levels.

When blocking of the increase of HDAC occurred by use of a HDAC inhibitor during alcohol withdrawal, levels of histone aceytlation and NPY expressions increased in the amygdala.

"Our findings suggest that HDAC inhibitors may have the potential as therapeutic agents in treating alcholism, " Pandey said.

The researchers concluded that the enzymes that are involved in remodeling of chromatin play an important part in the anxiety that comes with alcoholism withdrawal.

Related Links:
http://www.medicalnewstoday.com/articles/102871.php

http://www.medscape.com/viewarticle/521403_7

Sarah Siu (41520819)

Discovery Of Genetic Factor In Stress Response Variability

Inherited variations in the amount of an innate anxiety-reducing molecule help explain why some people can withstand stress better than others, according to a new study led by researchers at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH). "Stress response is an important variable in vulnerability to alcohol dependence and other addictions, as well as other psychiatric disorders," noted NIAAA Director Ting-Kai Li, M.D. "This finding could help us understand individuals' initial vulnerability to these disorders." Scientists led by David Goldman, M. D., chief of the NIAAA Laboratory of Neurogenetics, identified gene variants that affect the expression of a signaling molecule called neuropeptide Y (NPY). Found in brain and many other tissues, NPY regulates diverse functions, including appetite, weight, and emotional responses. "NPY is induced by stress and its release reduces anxiety," said Dr. Goldman. "Previous studies have shown that genetic factors play an important role in mood and anxiety disorders. In this study, we sought to determine if genetic variants of NPY might contribute to the maladaptive stress responses that often underlie these disorders." A report of the findings appears online in Nature. Analyses of human tissue samples led by researchers at NIAAA identified several NPY gene variants. Collaborations with NIH-supported scientists at the University of Michigan, University of Pittsburgh, University of Helsinki, University of Miami, University of Maryland, the University of California at San Diego, and Yale University, showed that these variants result in a range of different effects including altered levels of NPY in brain and other tissues, and differences in emotion and emotion-induced responses of the brain. The researchers evaluated the NPY gene variants' effects on brain responses to stress and emotion. Using functional brain imaging, they found that individuals with the variant that yielded the lowest level of NPY reacted with heightened emotionality to images of threatening facial expressions. "Metabolic activity in brain regions involved in emotional processing increased when these individuals were presented with the threatening images," explained Dr. Goldman. In another brain imaging experiment, people with the low level NPY variant were found to have a diminished ability to tolerate moderate levels of sustained muscular pain. Previous studies had shown that NPY's behavioral effects are mediated through interactions with opioid compounds produced by the body to help suppress pain, stress, and anxiety. "As shown by brain imaging of opioid function, these individuals released less opioid neurotransmitter in response to muscle discomfort than did individuals with higher levels of NPY," said Dr. Goldman. "Their emotional response to pain was also higher, showing the close tie between emotionality and resilience to pain and other negative stimuli." In a preliminary finding, the low level NPY gene variant was found to be more common than other variants among a small sample of individuals with anxiety disorders. The researchers also found that low level NPY expression was linked to high levels of trait anxiety. "Trait anxiety is an indication of an individual's level of emotionality or worry under ordinary circumstances," explained Dr. Goldman. The researchers conclude that these converging findings are consistent with NPY's role as an anxiety-reducing peptide and help explain inter-individual variation in resiliency to stress. "This inherited functional variation could also open up new avenues of research for other human characteristics, such as appetite and metabolism, which are also modulated by NPY," said Dr. Goldman.

By : Fazren Azmi(41558072)

Useful Links


· Health Site GuideReliable links to individual website pages with Anxiety information.http://www.healthsiteguide.com/modules.php?name=News&file=article&sid=
· I am Panicked .comInformation on anxiety and depression and the treatments available.http://www.iampanicked.com/
· Massage NetworkA worldwide listing of massage therapists dedicated to promoting and professionalizing massage and massage therapists.http://massagenetwork.com/
· Overcoming AnxietyInformation on a wide range of anxiety disorders and how to overcome them.http://www.overcominganxiety.org/
· Stress Focus.comInformation on the causes and methods of relieving stress.http://www.stressfocus.com/

Gene Variation Increases Asthma

Gene Variant Increases Asthma


Asthma is a common respiratory disease that affects nearly 155 million individuals worldwide. This disease causes chronic inflammation of the airways and restricts breathing, causes coughing and these symptoms can range from moderate to life threatening. Genetics are crucially important in understanding asthma to combat this debilitating disease and continual research is being conducted to find an answer to this genetic puzzle. There are over 100 genes that have been reported to be associated with asthma and 53 genes linked to this disease in one year alone. Research is now being undertaken to distinguish between genes that are directly related to the cause of asthma and those that combine with environmental factors.
One gene CHI3L1 ( chitinase 3-like 1 ) is now being studied closely as a tiny variation of this gene increases susceptibility to asthma by causing increased blood levels of YKL-40, a biomarker for asthma. YKL-40 are enzymes that are part of the bodies immune systems response to biologic polymers that are found in dust mites, insects and cockroaches all of which have been associated to asthma. Recent study on the levels of this enzyme in a genetically isolated community in South Dakota ( chosen as a excellent test pool , as they have similar but not identical genomes ) has shown that elevated YKL-40 levels were hereditary and that differences between individuals were down to genetic differences. It was documented that the people within the test pool who suffered from asthma were more likely to have a consistent variation of the gene CHI3L1. This variation changes one of the DNA base pairs from cytosine to guanine at the location -131CG within the gene.
After this was discovered other clinical studies were undertaken and resulting samples showed that those with cytosine (c) – cytosine (c) or CC configuration at the 131CG location were more likely to suffer from asthma. The lowest risk of asthma is identified with the GG configuration, while the CG configuration showed an intermediate risk.
The subsequent findings have prompted scientists to pursue drug development in an attempt to block the YKL-40 enzyme and thus lower the risk of asthma.
Source: http://www.medicalnewstoday.com/articles/
Lachlan Charles 41784161