Posts tagged science

ScienceDaily (June 7, 2012) — Scientists have discovered a new function for a protein that protects cells during injury and could eventually translate into treatment for conditions ranging from cardiovascular disease to Alzheimer’s.

Researchers report online June 7 in the journal Cell that a type of protein called thrombospondin activates a protective pathway that prevents heart cell damage in mice undergoing simulated extreme hypertension, cardiac pressure overload and heart attack.

"Our results suggest that medically this protein could be targeted as a way to help people with many different disease states where various organs are under stress,” said Jeffery Molkentin, PhD, lead investigator and a researcher at Cincinnati Children’s Hospital Medical Center and the Howard Hughes Medical Institute. "Although more study is needed to determine how our findings might be applied clinically, a possible therapeutic strategy could include a drug or gene therapy that induces overexpression of the protein in tissues or organs undergoing injury."

Thrombospondin (Thbs) proteins are produced by the body in cells where tissues are being injured, reconfigured or remodeled, such as in chronic cardiac disease. They appear in part of the cell’s internal machinery called the endoplasmic reticulum. There, Thbs triggers a stress response process to regulate production of other proteins and help correct or rid cells of proteins that misfold and lose their form and intended function. Misfolded proteins help drive tissue damage and organ dysfunction.

The researchers zeroed in on how one thrombospondin protein (Thbs4) activates cellular stress responses in mice bred to overexpress the protein in heart cells. They compared how the hearts of the Thbs4-positive mice responded to simulated stress and injury to mice not bred to overexpress cardiac-specific Thbs4.

Overexpression of Thbs4 had no effect on the animals prior to cardiac stress — although during simulated hypertension and cardiac infarction the protein reduced injury and protected them from death. Mice not bred for Thbs4 overexpression were extremely sensitive to cardiac injury, according to Molkentin, a member of the Division of Molecular Cardiovascular Biology and Cincinnati Children’s Heart Institute.

The researchers reported that overexpressed Thbs4 enhanced the ability of heart cells to secrete helpful proteins, resolve misfolded proteins and properly reconstruct extracellular matrix — connective tissues that help give the heart functional form and structural integrity.

Critical to the stress response process was Thbs4 activating and regulating a transcription factor called Aft6alpha. Transcription factors help decode genetic instructions of other genes to control their expression. In the case of Aft6alpha in the heart, it helps mediate repair processes. When Aft6alpha is activated by Thbs4, the endoplasmic reticulum in cells expands and the production of chaperone molecules and other repair proteins is enhanced.

Mice bred not to overexpress cardiac Thbs4 did not exhibit activated Aft6alpha or robust repair processes following cardiac injury, leading to their poor outcomes.

Molkentin said the research team continues to examine the Thbs-dependent stress response pathway to better understand the involved processes. This includes seeing how the pathway affects laboratory models of neurodegenerative diseases like Parkinson’s, Alzheimer’s and amyotrophic lateral sclerosis.

Source: Science Daily

June 7, 2012

The Huntington Study Group (HSG), under the leadership of Ray Dorsey, M.D. with Johns Hopkins Medical and Diana Rosas, M.D. with Massachusetts General Hospital, is conducting a clinical trial in Huntington’s disease (HD) throughout the United States and Australia, “A randomized, double-blind, placebo-controlled, study to assess the safety and tolerability, and efficacy of PBT2 in patients with early to mid-stage Huntington’s disease” comparing a 100 mg dose or 250 mg dose versus placebo. The HSG is a not-for-profit group of physicians and other clinical researchers who are experienced in the care of HD patients and dedicated to clinical research of the disease. This trial is sponsored by Prana Biotechnology Limited (Melbourne, Australia) and is being managed by the University of Rochester Medical Center.

Huntington’s disease is an inherited neurodegenerative disease which affects over 30,000 people in both the United States and Australia. HD is characterized by brain cell death that usually begins between the ages of 30 to 50, and results in motor, cognitive and behavioral signs and symptoms. While there are medications to help relieve some of the disease symptoms, there is no known treatment to address the cognitive impairment associated with HD.

Research has shown that normally occurring metals in the brain play a significant role in diseases such as Alzheimer’s disease and more recently, HD. Researchers at Prana Biotechnology are identifying drugs designed to interrupt interactions between these biological metals and target proteins in the brain, to prevent deterioration of brain cells. One of the chemical compounds, called PBT2, has shown in animal models, and as well as in a small group of patients with Alzheimer’s disease, that it may improve cognition. There is some indication in animal models of HD, that the drug may improve motor function and control, increase life span and reduce the amount of brain cell degeneration. Based on these results, Prana is investigating whether the drug will have similar effects with HD patients.

Reach2HD will evaluate how safe and well tolerated PBT2 is at a dose of 100 mg or 250 mg a day compared to a placebo over six months. The trial will also measure whether there is an effect on cognitive abilities as well as other HD symptoms including motor and overall functioning of individuals with HD.

"We are excited to work with Prana to investigate the safety and tolerability of an interesting and innovative experimental treatment for Huntington’s disease, PBT2," said Dorsey. "We have few treatment options for Huntington disease, and none for cognition. We hope this is a step to addressing this large unmet need for patients and their families."

Provided by University of Rochester Medical Center

Source: medicalxpress.com

June 7, 2012

The Allen Institute for Brain Science announced today its latest public data release, enhancing online resources available via the Allen Brain Atlas data portal and expanding its application programming interface (API).

With this release, the Allen Institute has expanded access to its data and services via the Allen Brain Atlas API and added new data and feature enhancements to four atlas resources: the Allen Human Brain Atlas, the Allen Mouse Brain Connectivity Atlas, the Allen Developing Mouse Brain Atlas, and the Allen Mouse Brain Atlas. In addition, two new video tutorials have been added to the Institute’s tutorial library.

The Allen Human Brain Atlas, a multi-modal, three-dimensional map of the human brain that integrates anatomical and gene expression data throughout the adult human brain, has been expanded to include gene expression data from brains of autistic individuals, allowing scientists to compare disease and control states. In addition, the Atlas contains new features to facilitate search, navigation, and download of data.

The Allen Mouse Brain Connectivity Atlas is a three-dimensional, high-resolution map of neural connections throughout the mouse brain. Today’s data release expands the set of available high-resolution images of axonal projections and adds multiplanar viewing capabilities, offering a first step towards three-dimensional visualization of neural connectivity throughout the mouse brain. This foundational map will help scientists understand how the brain is wired, offering new insights into how the brain works and what goes awry in brain diseases and disorders.

Additionally, the Allen Mouse Brain Atlas and the Allen Developing Mouse Brain Atlas have been updated with new search capabilities based on additional data annotation, allowing users to explore the gene expression data in new ways.

Application Programming Interface (API)

To broaden the user community and enable further innovation, the Allen Institute has expanded access to its data and services via the Allen Brain Atlas API, now offering access to data from across the suite of Allen Brain Atlas resources. The Allen Brain Atlas API provides the programming community with under-the-hood access to the Allen Institute’s vast datasets, sample applications and programming solutions for data searches and download, as well as opportunities for discovery and creation of new applications or data representations. This release coincides with the Allen Brain Atlas Hackathon, an elite programming event to be held later this month.

Available data in the Allen Brain Atlas API includes high-resolution images, 3-D expression summaries, primary microarray and RNA-sequencing results, and MRI and DTI files from across the Institute’s suite of atlas resources. Services offered by the Allen Brain Atlas API include RESTful model access to retrieve all experimental information; image download service for all gene expression, connectivity, histology and atlas data; as well as API access to various integrated search services.

Provided by Allen Institute for Brain Science

Source: medicalxpress.com

ScienceDaily (June 7, 2012) — Scientists at the Gladstone Institutes have for the first time transformed skin cells — with a single genetic factor — into cells that develop on their own into an interconnected, functional network of brain cells. The research offers new hope in the fight against many neurological conditions because scientists expect that such a transformation — or reprogramming — of cells may lead to better models for testing drugs for devastating neurodegenerative conditions such as Alzheimer’s disease.

Rendering of neural network. Scientists at the Gladstone Institutes have for the first time transformed skin cells — with a single genetic factor — into cells that develop on their own into an interconnected, functional network of brain cells. (Credit: © nobeastsofierce / Fotolia)

This research comes at a time of renewed focus on Alzheimer’s disease, which currently afflicts 5.4 million people in the United States alone — a figure expected to nearly triple by 2050. Yet there are no approved medications to prevent or reverse the progression of this debilitating disease.

In findings appearing online June 7 in Cell Stem Cell, researchers in the laboratory of Gladstone Investigator Yadong Huang, MD, PhD, describe how they transferred a single gene called Sox2 into both mouse and human skin cells. Within days the skin cells transformed into early-stage brain stem cells, also called induced neural stem cells (iNSCs). These iNSCs began to self-renew, soon maturing into neurons capable of transmitting electrical signals. Within a month, the neurons had developed into neural networks.

"Many drug candidates — especially those developed for neurodegenerative diseases — fail in clinical trials because current models don’t accurately predict the drug’s effects on the human brain," said Dr. Huang, who is also an associate professor of neurology at the University of California, San Francisco (UCSF), with which Gladstone is affiliated. "Human neurons — derived from reengineered skin cells — could help assess the efficacy and safety of these drugs, thereby reducing risks and resources associated with human trials."

Dr. Huang’s findings build on the work of other Gladstone scientists, starting with Gladstone Investigator, Shinya Yamanaka, MD, PhD. In 2007, Dr. Yamanaka used four genetic factors to turn adult human skin cells into cells that act like embryonic stem cells — called induced pluripotent stem cells.

Also known as iPS cells, these cells can become virtually any cell type in the human body — just like embryonic stem cells. Then last year, Gladstone Senior Investigator Sheng Ding, PhD, announced that he had used a combination of small molecules and genetic factors to transform skin cells directly into neural stem cells. Today, Dr. Huang takes a new tack by using one genetic factor — Sox2 — to directly reprogram one cell type into another without reverting to the pluripotent state.

Avoiding the pluripotent state as Drs. Ding and Huang have done is one approach to avoiding the potential danger that “rogue” iPS cells might develop into a tumor if used to replace or repair damaged organs or tissue.

"We wanted to see whether these newly generated neurons could result in tumor growth after transplanting them into mouse brains," said Karen Ring, UCSF Biomedical Sciences graduate student and the paper’s lead author. "Instead we saw the reprogrammed cells integrate into the mouse’s brain — and not a single tumor developed."

This research, which was performed at the Roddenberry Center for Stem Cell Biology and Medicine at Gladstone, has also revealed the precise role of Sox2 as a master regulator that controls the identity of neural stem cells. In the future, Dr. Huang and his team hope to identify similar regulators that guide the development of specific neural progenitors and subtypes of neurons in the brain.

"If we can pinpoint which genes control the development of each neuron type, we can generate them in the petri dish from a single sample of human skin cells," said Dr. Huang. "We could then test drugs that affect different neuron types — such as those involved in Parkinson’s disease — helping us to put drug development for neurodegenerative diseases on the fast track."

Source: Science Daily

ScienceDaily (June 7, 2012) — A study led by Karolinska Institutet in Sweden reports for the first time the positive effects of an active vaccine against Alzheimer’s disease. The new vaccine, CAD106, can prove a breakthrough in the search for a cure for this seriously debilitating dementia disease. The study is published in the scientific journal Lancet Neurology.

A study led by Karolinska Institutet in Sweden reports for the first time the positive effects of an active vaccine against Alzheimer’s disease. (Credit: © Tyler Olson / Fotolia)

Alzheimer’s disease is a complex neurological dementia disease that is the cause of much human suffering and a great cost to society. According to the World Health Organisation, dementia is the fastest growing global health epidemic of our age. The prevailing hypothesis about its cause involves APP (amyloid precursor protein), a protein that resides in the outer membrane of nerve cells and that, instead of being broken down, form a harmful substance called beta-amyloid, which accumulates as plaques and kills brain cells.

There is currently no cure for Alzheimer’s disease, and the medicines in use can only mitigate the symptoms. In the hunt for a cure, scientists are following several avenues of attack, of which vaccination is currently the most popular. The first human vaccination study, which was done almost a decade ago, revealed too many adverse reactions and was discontinued. The vaccine used in that study activated certain white blood cells (T cells), which started to attack the body’s own brain tissue.

The new treatment, which is presented in Lancet Neurology, involves active immunisation, using a type of vaccine designed to trigger the body’s immune defence against beta-amyloid. In this second clinical trial on humans, the vaccine was modified to affect only the harmful beta-amyloid. The researchers found that 80 per cent of the patients involved in the trials developed their own protective antibodies against beta-amyloid without suffering any side-effects over the three years of the study. The researchers believe that this suggests that the CAD106 vaccine is a tolerable treatment for patients with mild to moderate Alzheimer’s. Larger trials must now be conducted to confirm the CAD106 vaccine’s efficacy.

Source: Science Daily

ScienceDaily (June 7, 2012) — Researchers at Columbia University Medical Center (CUMC) have identified a brain receptor that appears to play a central role in regulating appetite. The findings, published June 7 in the online edition of Cell, could lead to new drugs for preventing or treating obesity.

"We’ve identified a receptor that is intimately involved in regulating food intake," said study leader Domenico Accili, MD, professor of Medicine at CUMC. "What is especially encouraging is that this receptor is belongs to a class of receptors that turn out to be good targets for drug development, making it a highly ‘druggable’ target. In fact, several existing medications already seem to interact with this receptor. So, it’s possible that we could have new drugs for obesity sooner rather than later."

In their search for new targets for obesity therapies, scientists have focused on the hypothalamus, a tiny brain structure that regulates appetite. Numerous studies suggest that the regulatory mechanism is concentrated in neurons that express a neuropeptide, or brain modulator, called AgRP. But the specific factors that influence AgRP expression are not known.

The CUMC researchers found new clues to appetite control by tracing the actions of insulin and leptin. Both hormones are involved in maintaining the body’s energy balance, and both are known to inhibit AgRP. “Surprisingly, blocking either the insulin or leptin signaling pathway has little effect on appetite,” says Dr. Accili. “We hypothesized that both pathways have to be blocked simultaneously in order to influence feeding behavior.”

To test their hypothesis, the researchers created a strain of mice whose AgRP neurons lack a protein that is integral to both insulin and leptin signaling. As the researchers hypothesized, removing this protein — Fox01 — had a profound effect on the animals’ appetite. “Mice that lack Fox01 ate less and were leaner than normal mice,” said lead author Hongxia Ren, PhD, associate research scientist in Medicine. “In addition, the Fox01-deficient mice had better glucose balance and leptin and insulin sensitivity — all signs of a healthier metabolism.”

Since Fox01 is a poor drug target, the researchers searched for other ways to inhibit the action of this protein. Using gene-expression profiling, they found a gene that is highly expressed in mice with normal AgRP neurons but is effectively silenced in mice with Fox01-deficient neurons. That gene is Gpr17 (for G-protein coupled receptor 17), which produces a cell-surface receptor called Gpr17.

To confirm that the receptor is involved in appetite control, the researchers injected a Gpr17 activator into normal mice, and their appetite increased. Conversely, when the mice were given a Gpr17 inhibitor, their appetite decreased. Similar injections had no effect on Fox01-deficient mice.

According to Dr. Accili, there are several reasons why Gpr17, which is also found in humans, would be a good target for anti-obesity medications. Since Grp17 is part of the so-called G-protein-coupled receptor family, it is highly druggable. About a third of all existing drugs work through G-protein-coupled receptors. In addition, the receptor is abundant in AgRP neurons but not in other neurons, which should limit unwanted drug side effects.

Source: Science Daily

ScienceDaily (June 7, 2012) — Increasing the spacing between characters and words in a text improves the speed and quality of dyslexic children’s reading, without prior training. They read 20% faster on average and make half as many errors. This is the conclusion reached by a French-Italian research team, jointly headed by Johannes Ziegler of the Laboratoire de Psychologie Cognitive (CNRS/Aix-Marseille Université).

Increasing the spacing between characters and words in a text improves the speed and quality of dyslexic children’s reading, without prior training. (Credit: © Johannes Ziegler, courtesy CNRS)

These results were published 4 June 2012 in the Proceedings of the National Academy of Science (PNAS). In parallel, the team has developed an iPad/iPhone application, available under the name “DYS.” It allows both parents and children to modify the spacing between letters and thus test the benefits of these changes on reading. This will enable researchers to collect large-scale, real time data, which they will then analyze and study.

Dyslexia is a learning disability that impairs an individual’s capacity to read and is linked to difficulty in identifying letters, syllables and words — despite suitable schooling and in the absence of intellectual or sensorial deficiencies. Dyslexia, which often causes writing problems, affects on average one child in every class and 5% of the world’s population.

In this study, the researchers tested the effects of letter spacing on the reading ability of 54 dyslexic Italian and 40 dyslexic French children aged between 8 and 14 years. The children had to read a text composed of 24 sentences, in which the spacing was either normal or wider than usual. The results showed that wider spacing enabled the children to improve their reading both in terms of speed and precision. On average, they read 20% faster and made half as many errors. This progress could stem from the fact that dyslexic children are particularly sensitive to “perceptual crowding,” in other words the visual masking of each individual letter by those surrounding it. The results of this study show that this crowding effect may be reduced by spacing letters apart.

This finding opens interesting perspectives in the field of dyslexia treatment techniques. Indeed, reading better means reading more — yet it takes one year for a dyslexic child to read what a “normal reader” reads in two days. This is because reading can be “torture” for dyslexic children, whose decoding difficulties cause to stumble, putting them off reading on a regular basis. The researchers have found a simple and efficient “trick” that helps these children break the vicious circle and correctly read more words in less time.

An iPad/iPhone application known as “DYS” has been developed in parallel with these research results by Stéphane Dufau, CNRS research engineer at the Laboratoire de Psychologie Cognitive. Available initially in French and English and downloadable free of charge from Apple Store, it enables both parents and children to adjust the spacing between letters and to test the benefits of such modifications on reading. The researchers for their part hope to be able to collect large-scale data that will allow them to quantify and analyze whether optimal spacing exists as a function of the subject’s age and reading level.

Download available: http://itunes.apple.com/us/app/dys-help-people-with-dyslexia/id529867852?mt=8

Source: Science Daily

ScienceDaily (June 6, 2012) — Even when brain injury is so subtle that it can only be detected by an ultra-sensitive imaging test, the injury might predispose soldiers in combat to post-traumatic stress disorder, according to a University of Rochester Medical Center study.

The research is important for physicians who are caring for troops in the years following deployment, as they try to untangle the symptom overlap between PTSD and mild traumatic brain injury (mild TBI) and provide the appropriate treatment. Until now, the nature of the interaction between TBI and PTSD was unclear. URMC researchers believe they are the first to find an association that can be demonstrated with advanced imaging techniques.

The study is published online by the Journal of Head Trauma Rehabilitation.

"Most people believe that, to a large extent, chronic stress from intense combat experiences triggers PTSD. Our study adds more information by suggesting that a physical force such as exposure to a bomb blast also may play a role in the genesis the syndrome," said lead author Jeffrey J. Bazarian, M.D., M.P.H., associate professor of Emergency Medicine at URMC, and a member of the 2007 Institute of Medicine committee that investigated brain injuries among war veterans.

By 2008 it was estimated that 320,000 troops suffered concussions in Iraq and Afghanistan. Bazarian’s research involved 52 war veterans from western New York who served in combat areas between 2001 and 2008. Approximately four years after their final tour of duty, researchers asked each veteran about PTSD symptoms, blast exposures, mild concussions, and combat experiences.

Researchers measured combat stress in the study participants with a standard Walter Reed Institute of Research Combat Experiences Survey, which asks about the intensity of deployment duties (such as handling or uncovering remains), exposure to explosive devices, vehicle accidents, falls or assaults, and events such as being ambushed or knowing someone who was seriously injured or killed. The investigators also performed standard MRI testing, as well as a more sensitive test called diffusion tensor imaging, or DTI. The latter has been used to detect axonal injury, a type of neuronal damage that occurs during a concussion.

Results showed that 30 of the 52 New York veterans suffered at least one mild traumatic brain injury, and seven reported having more than one. Sixty percent of the veterans were exposed to one or more explosive blasts.

All 52 veterans had one or more PTSD symptoms, and 15 met the formal criteria for PTSD, which is a devastating psychiatric illness. The severity of veterans’ PTSD symptoms correlated with the amount of axonal injury seen on the DTI scans.

In addition, five of the 52 veterans showed abnormalities on standard MRI scans, and their PTSD severity was much worse than the 46 veterans with normal MRIs.

Interestingly, PTSD severity did not correlate with the clinical diagnosis of mild TBI. This suggests that subtle brain injury can occur without producing the loss of consciousness or amnesia that is typically associated with diagnosis of mild TBI, and that this injury may make a person more vulnerable to psychiatric illness when coupled with extreme chronic stress.

"Based on our results, it looks like the only way to detect this injury is with DTI/MRI," Bazarian said. "While it may not be feasible due to costs and limited availability of some neuro-imaging tests to screen thousands of service members for brain injury, our study highlights the pressing need to develop simpler tests that are accurate and practical, that correlate with brain injury."

Source: Science Daily

ScienceDaily (June 6, 2012) — Psychoactive medications in water affect the gene expression profiles of fathead minnows in a way that mimics the gene expression patterns associated with autism spectrum disorder in genetically susceptible humans, according to research published June 6 in the open access journal PLoS ONE. These results suggest a potential environmental trigger for autism spectrum disorder in this vulnerable population, the authors write.

The researchers, led by Michael A. Thomas of Idaho State University, exposed the fish to three psychoactive pharmaceuticals — fluoxetine, a selective serotonin reuptake inhibitor, or SSR1; venlafaxine, a serotonin-norepinephrine reuptake inhibitor, and carbamazepine, used to control seizures — at concentrations comparable to the highest estimated environmental levels.

They found that the only gene expression patterns affected were those associated with idiopathic autism spectrum disorders, caused by genetic susceptibility interacting with unknown environmental triggers. These results suggest that exposure to environmental psychoactive pharmaceuticals may play a role in the development of autism spectrum disorder in genetically predisposed individuals.

Lead researcher Michael A. Thomas remarks, “While others have envisioned a causal role for psychotropic drugs in idiopathic autism, we were astonished to find evidence that this might occur at very low dosages, such as those found in aquatic systems.”

Source: Science Daily

ScienceDaily (June 6, 2012) — An Indiana University biologist has shown that natural variation in measures of the brain’s ability to process steroid hormones predicts functional variation in aggressive behavior.

Researchers studied the behaviors of free-living dark-eyed juncos during breeding season to measure variations in aggressiveness. (Credit: Image courtesy of Indiana University)

The new work led by Kimberly A. Rosvall, a postdoctoral fellow and assistant research scientist in the IU Bloomington College of Arts and Sciences’ Department of Biology, has found strong and significant relationships between aggressive behavior in free-living birds and the abundance of messenger RNA in behaviorally relevant brain areas for three major sex steroid processing molecules: androgen receptor, estrogen receptor and aromatase.

"Individual variation is the raw material of evolution, and in this study we report that free-living birds vary in aggression and that more aggressive individuals express higher levels of genes related to testosterone processing in the brain," she said. "We’ve long hypothesized that the brain’s ability to process steroids may account for individual differences in hormone-mediated behaviors, but direct demonstrations are rare, particularly in unmanipulated or free-living animals."

Rosvall said the study shows that aggression is strongly predicted by individual variation in gene expression of the molecules that initiate the genomic effects of testosterone. The new work, “Neural sensitivity to sex steroids predicts individual differences in aggression: implications for behavioral evolution,” was published June 6 in Proceedings of The Royal Society B.

The findings are among the first to show that individual variation in neural gene expression for three major sex steroid processing molecules predicts individual variation in aggressiveness in both sexes in nature, results that should have broad implications for understanding the mechanisms by which aggressive behavior may evolve.

"On the one hand, we have lots of evidence to suggest that testosterone is important in the evolution of all kinds of traits," Rosvall noted. "On the other hand, we know that individual variation is a requirement for natural selection, but individual variation in testosterone does not always predict behavior. This conundrum has led to debate among researchers about how hormone-mediated traits evolve."

To find such strong relationships between behavior and individual variation in the expression of genes related to hormone-processing is exciting because it tells scientists that evolution could shape behavior via changes in the expression of these genes, as well as via changes in testosterone levels themselves.

The team measured natural variation in aggressiveness toward the same sexes in male and female free-living dark-eyed juncos (Junco hyemalis) early in the breeding season. The dark-eyed junco is a North American sparrow that is well studied with respect to hormones, behavior and sex differences. By comparing individual differences in aggressiveness (flyovers or songs directed at intruders) to circulating levels of testosterone and to neural gene expression for the three major sex steroid processing molecules, the researchers were able to quantify measures of sensitivity to testosterone in socially relevant brain areas: the hypothalamus, the ventromedial telencephalon and the right posterior telencephalon.

Their results suggest selection could shape the evolution of aggression through changes in the expression of androgen receptor, estrogen receptor and aromatase in both males and females, to some degree independently of circulating levels of testosterone. They found, for example, that males that sing more songs at an intruder have more mRNA for aromatase and estrogen receptor in the posterior telencephalon, and also that males and females that dive-bomb an intruder more frequently have more androgen receptor, estrogen receptor and aromatase mRNA in brain tissues including the medial amygdala, an area of the brain that’s known to control aggression in rodents and other birds. mRNA are single-stranded copies of genes that are translated into protein molecules.

The work reveals there is ample variation in hormone signal and in gene expression on which selection may act to affect aggressiveness. It also establishes a prerequisite for the evolution of testosterone-mediated characteristics through changes in localized gene expression for the key molecules that process sex steroids, and suggests that trait evolution can occur with some degree of independence from circulating testosterone levels.

"Researchers have thought this was probably the case for about a hundred years, based on a lot of really important work that uses experimental manipulations like castration or hormone replacement," Rosvall said. "But very few people have looked to see if individuals actually do vary in expression of these genes, and whether this individual variation means anything, in terms of an animal’s behavior. Our work shows that it does."

The new insights into how neuroendocrine mechanisms of aggression may be modified as populations diverge into species also offer opportunities for future research, including trying to determine whether genes that are up- or down-regulated in response to environmental stimuli may be the same genes that contribute to the evolution of certain traits and characteristics.

Source: Science Daily