Human Alcohol Consumption Patterns Mimicked By New Strain Of Lab Mice

Main Category: Alcohol / Addiction / Illegal Drugs
Also Included In: Genetics
Article Date: 15 Dec 2011 - 0:00 PST

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A line of laboratory mice developed by a researcher from the School of Science at Indiana University-Purdue University Indianapolis (IUPUI) drinks more alcohol than other animal models and consumes it in a fashion similar to humans: choosing alcohol over other options and binge drinking.

In previous Animal models researchers found that the animals did not get as drunk as the new strain unless alcohol was the only choice of fluids, or alcohol was administered by the experimenter. When given the option, previously bred mouse lines continued to drink water even when they ccould select alcohol.

These new mice, selectively bred over 40 generations at the School of Science at IUPUI to prefer alcohol over all other choices, will help researchers explore new aspects of the behavioral and genetic determinants of alcoholism.

In a study published online ahead of print in the journal Addiction Biology , senior author Nicholas Grahame, Ph.D., associate professor of psychology in the School of Science at IUPUI, reports on the mice he has bred since 1997. The rodents reach blood-alcohol levels of more than 260 mg/dl of alcohol daily, over three times the equivalent of the human legal driving limit and the approximate consumption level that the severest human alcoholics attain.

"The free-choice drinking demonstrated by the new mouse line provides a unique opportunity to study the excessive intake that often occurs in alcohol-dependent individuals and to explore the predisposing factors for excessive consumption, as well as the development of physiological, behavioral and toxicological outcomes following alcohol exposure," says Grahame, who is a biopsychologist specializing in alcoholism.

According to the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, an estimated 17.6 million Americans abuse alcohol or are alcohol dependent. Alcohol abuse and alcoholism can be treated but cannot be cured.

Mice share 80 percent of their genes with humans, so they are an excellent model to study alcoholism, a disease with a strong genetic component. The risk of developing alcoholism is known to be influenced by lifestyle. Animal models allow researchers to employ methods that they are unable to use in humans.

"This line of high-alcohol-seeking mice should be able to give us a better understanding of the basic brain mechanism involved in alcohol consumption as well as greater insight into the toxic effects on the brain, with the goal of developing therapies," said Grahame, whose research focuses on behavioral genetics and behavioral pharmacology.

As with humans, the mice become intoxicated when the pace of alcohol consumption is faster than the liver can eliminate it. Typically it takes six or seven hours of continuous alcohol drinking for the new breed of mice to reach the highest levels of intoxication.

Doctoral candidate Liana M. Matson is a co-author of the study. She has conducted research focusing on when the mice drink and determined that they are nocturnal drinkers. This knowledge enabled the mice's blood-alcohol levels to be tested when at their highest level.

Undergraduate School of Science students Amy Buckingham and Nick Villalta assisted in the research by measuring intake and blood-alcohol levels in the new strain of high-alcohol-seeking mice. In a related study, they analyzed how drunk the mice became by testing how they performed on a balance beam.

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
Visit our alcohol / addiction / illegal drugs section for the latest news on this subject. Development of the mouse line and the Addiction Biology study were funded by NIAAA and the School of Science at IUPUI.
Indiana University-Purdue University Indianapolis School of Science Please use one of the following formats to cite this article in your essay, paper or report:

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Gene Inheritance Patterns Influence Age Of Diagnosis In BRCA Families

Main Category: Breast Cancer
Also Included In: Genetics;  Ovarian Cancer
Article Date: 13 Dec 2011 - 1:00 PST

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Women who inherit the cancer genes BRCA1 or BRCA2 from their paternal lineage may get a diagnosis a decade earlier than those women who carry the cancer genes from their mother and her ancestors, according to a new study by researchers at the North Shore-LIJ Health System's Monter Cancer Center in Lake Success, NY. The findings were reported at the San Antonio Breast Cancer Symposium.

Iuliana Shapira, MD, North director of cancer genetics, and her colleagues conducted a retrospective review of 130 breast or ovarian cancer patients with the BRCA1 or BRCA2 mutations. They chose only those patients who knew the parent of origin. In other words, they could follow along their family tree to see where the breast cancer gene originated from. Some of their families had their own genetic tests done. For others, it was a matter of following the family pedigree.

As expected, a person had a 50-50 chance of getting a mutant BRCA gene from their mother or their father's branch that carried the mutation. It is an autosomal dominant mutation. Looking at the family maps revealed some surprising findings. Contrary to the notion that the BRCA mutations are associated more commonly with Ashkenazi Jews, the scientists found that the BRCA mutations were also in families of Irish and Jamaican descent. "No one had ever conducted a study to look at the parent-of-origin effects," said Dr. Shapira. "Genetic diseases may display parent-of-origin effects. In such cases, the risk depends on the specific parent or origin allele. Cancer penetrance in mutations carriers may be determined by the parent origin of BRCA mutation."

They analyzed 1,889 consecutive (136 ovarian + 1753 breast) breast (BrCa) or ovarian cancer (OvCa) patients presenting for treatment at the Monter Cancer Center between 2007 and 2010. In 130 patients with BRCA 1 or 2 mutations the parent of origin for the mutation was known. Of the 130 patients, two had both BRCA1 and BRCA2 mutated paternally inherited disease and were excluded from this analysis. Of the breast cancer patients: 28 patients had paternal and 29 had maternal BRCA1 mutations, 24 had paternal and 21 had maternal BRCA 2 mutations. Of the ovarian cancer patients, six had paternal and 10 had maternal BRCA1 mutations; seven had paternal and three had maternal BRCA2 mutations.

In carriers of BRCA mutations, the mean age at diagnosis for ovarian cancer was 51 (range 21-70) and for breast cancer was 43 (range 24-78). But when they compared the mean age at diagnosis in the maternal versus paternal inheritance, they were surprised to find that breast cancer patients with a BRCA1 maternal inheritance, the age of diagnosis was on average around 45. By comparison, women with BRCA1 paternal inheritance were diagnosed around 38. For breast cancer BRCA2 maternal inheritance, the average age of diagnosis was 50 compared to 41 years old for those with a BRCA2 paternal inheritance.

There was no significant difference between paternal and maternal age of ovarian cancer diagnosis of BRCA1 or BRCA2 mutations.

"If this observation is duplicated in larger cohorts the results will have important implications for recommendation of surgical risk reduction in BRCA mutation carriers," said Dr. Shapira. "That would mean that doctors might think about watching and waiting in young woman with BRCA mutations inherited from her mother's family and being more aggressive in young women who inherited the mutation from their father's side."

Article adapted by Medical News Today from original press release. Click 'references' tab above for source.
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Long-Term Imaging Reveals Intriguing Patterns Of Human Brain Maturation

Main Category: Neurology / Neuroscience
Article Date: 09 Dec 2011 - 0:00 PST

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Neuroimaging has provided fascinating insight into the dynamic nature of human brain maturation. However, most studies of developmental changes in brain anatomy have considered individual locations in relative isolation from all others and have not characterized relationships between structural changes in different parts of the developing brain. Now, new research describes the first comprehensive study of coordinated anatomical maturation within the developing human brain. The study, published by Cell Press in the December 8 issue of the journal Neuron, reveals that functionally connected brain regions mature together and uncovers fascinating sex-specific differences in brain development.

"Understanding patterns of structural change in the developing human brain is a challenge because the types of change that we can detect using neuroimaging unfold rather slowly," explains lead study author, Dr. Armin Raznahan, from the National Institutes of Mental Health in Bethesda, Maryland. "So, we drew from the largest and longest-running longitudinal neuroimaging study of human brain maturation, where brain changes were tracked for over several years in the same set of individuals, to analyze patterns of correlated anatomical change across the sensitive developmental window of late childhood, adolescence, and early adulthood."

Dr. Raznahan and colleagues examined the thickness of the cortex because it can be reliably measured and its developmental changes have been described in detail. The cortex is a sheet of neural tissue that covers the surface of the brain and plays a key role in thought, language, memory and consciousness.

The researchers discovered that rates of structural maturation were highly coordinated in the cortex and that regions which were functionally connected to each other also exhibited tightly coupled patterns of maturation. Interestingly, the researchers also observed that maturational coupling within the brain regions crucial for complex decision making differed between males and females.

"Our study represents the first ever investigation of correlated anatomical maturation in the developing human brain and shows that rates of structural cortical development in different cortical regions are highly organized with respect to one another," concludes Dr. Raznahan. "By providing the first link between cortical connectivity and the coordination of cortical development, we reveal a previously unseen property of healthy brain maturation, which may represent a target for neurodevelopmental disease processes and a substrate for sexually dimorphic behavior in adolescence."

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Cell Press. "Long-Term Imaging Reveals Intriguing Patterns Of Human Brain Maturation." Medical News Today. MediLexicon, Intl., 9 Dec. 2011. Web.
9 Dec. 2011. APA

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