Alternative antibody architecture

The complex genomic apparatus for making lampreys' antibody-like receptors

The age of blood

Investigating how long blood can be stored before the benefit of transfusion is compromised

PTH for stroke: stem cells lite

Spur the body's regenerative agents to emerge from the bone marrow

Yerkes National Primate Research Center

Maturing brain flips function of amygdala in regulating stress hormones

In contrast to evidence that the amygdala stimulates stress responses in adults, researchers at Yerkes National Primate Research Center, Emory University have found that the amygdala has an inhibitory effect on stress hormones during the early development of nonhuman primates.

The results are published this week in Journal of Neuroscience.

The amygdala is a region of the brain known to be important for responses to threatening situations and learning about threats. Alterations in the amygdala have been reported in psychiatric disorders such as depression, anxiety disorders like PTSD, schizophrenia and autism spectrum disorder. However, much of what is known about the amygdala comes from research on adults.

“Our findings fit into an emerging theme in neuroscience research: that during childhood, there is a switch in amygdala function and connectivity with other brain regions, particularly the prefrontal cortex,” says Mar Sanchez, PhD, neuroscience researcher at Yerkes and associate professor of psychiatry and behavioral sciences at Emory University School of Medicine. The first author of the paper is postdoctoral fellow Jessica Raper, PhD.

Some notable links on the amygdala:

*An effort to correct simplistic views of amygdala as the “fear center” of the brain

*Collection of papers mentioning patient SM, an adult human with an amygdala lesion

*Recent Nature Neuroscience paper on amygdala’s role in appetite control

*Evidence for changing amygdala-prefrontal connectivity in humans during development Read more

Posted on by Quinn Eastman in Neuro Leave a comment

Two heavy hitters in this week’s Nature

Two feature articles in Nature this week on work by Emory scientists.

One is from Virginia Hughes (Phenomena/SFARI/MATTER), delving into Kerry Ressler’s and Brian Dias’ surprising discovery in mice that sensitivity to a smell can be inherited, apparently epigenetically. Coincidentally, Ressler will be giving next week’s Dean’s Distinguished Faculty lecture (March 12, 5:30 pm at the School of Medicine).

Another is from Seattle global health writer Tom Paulson, on immunologist Bali Pulendran and using systems biology to unlock new insights into vaccine design.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Talkin’ about epigenetics

This intriguing research has received plenty of attention,  both when it was presented at the Society of Neuroscience meeting in the fall and then when the results were published in Nature Neuroscience.

The short summary is: researchers at Yerkes National Primate Research Center found that when a mouse learns to become afraid of a certain odor, his or her pups will be more sensitive to that odor, even though the pups have never encountered it. Both the parent mouse and pups have more space in the smell-processing part of their brains, called the olfactory bulb, devoted to the odor to which they are sensitive.

[Note: a feature on a similar phenomenon, transgenerational inheritance of the effects of chemical exposure, appeared in Science this week]

Somehow information about the parent’s experiences is being inherited. But how? Brian Dias and Kerry Ressler are now pursuing followup experiments to firmly establish what’s going on. They discuss their research in this video:

 

Posted on by Quinn Eastman in Neuro Leave a comment

Default daydreaming linked to Alzheimer’s amyloid

Cut the daydreaming, and you can lessen the neurodegenerative burden on your brain? Surprising new research suggests that how we use our brains may influence which parts of the brain are most vulnerable to amyloid-beta (Aβ), which forms plaques in the brain in Alzheimer’s disease.

Lary Walker, PhD, has been investigating why amyloid accumulation seems to lead to Alzheimer's in humans but not non-human primates

In the June issue of Nature Neuroscience, Yerkes National Primate Research Center scientist Lary Walker and Mathias Jucker from the Hertie Institute for Clinical Brain Research in Tübingen, Germany summarize intriguing recent research on regional brain activity and Aβ accumulation.

Neuroscientists have described a set of interconnected brain regions called the “default mode network,” which appear to be activated during activities such as introspection, memory retrieval, daydreaming and imagination. When a person engages in an externally directed task, such as reading, playing a musical instrument, or solving puzzles, activity in the default network decreases.

The Nature Neuroscience paper, from David Holtzman and colleagues at Washington University St. Louis, suggests prolonged metabolic activation of the default-mode network in mice can render that system vulnerable to Aβ by accelerating Aβ deposition and plaque growth.

This line of research turns the “use it or lose it” idea upside-down. Use the default network too much, and the effect may be harmful. Walker and Jucker suggest why education, for example, appears to head off Alzheimer’s in epidemiological studies: by getting the brain involved in non-default/externally directed mode activity.

This idea has additional consequences that can be tested in the clinic. For example, by increasing metabolism in default-mode regions of the brain, prolonged wakefulness caused by sleep disorders might increase Aβ burden.

Walker and Jucker conclude: “Meanwhile, perhaps the best strategy for lessening soluble Aβ in the default mode network may be simply to work diligently, play hard and sleep well.”

 

Posted on by Quinn Eastman in Neuro 2 Comments

Brain enhancement: can and should we do it?

The Emory Center for Ethics and Emory’s Neuroscience Graduate Program recently co-hosted a symposium discussing the ethics of brain-enhancing technologies, both electronic and pharmacological.

Georgia Tech biomedical engineer Steve Potter explained his work harnessing the behavior of neurons grown on a grid of electrodes. The neurons, isolated from rats, produce bursts of electrical signals in various patterns, which can be “tuned” by the inputs they receive.

“The cells want to form circuits and wire themselves up,” he said.

As for future opportunities, he cited the technique of deep brain stimulation as well as clinical trials in progress, including one testing technology developed by the company Neuropace that monitors the brain’s electrical activity for the purpose of suppressing epileptic seizures. Similar technology is being developed to help control prosthetic limbs and could also promote recovery from brain injury or stroke, he said. Eventually, electrical stimulation that is not modulated according to feedback from the brain will be seen as an overly blunt instrument, even “barbaric,” he said.

Mike Kuhar, a neuroscientist at Yerkes National Primate Research Center, introduced the topic of cognitive enhancers or “smart drugs.” He described one particular class of proposed cognitive enhancers, called ampakines, which appear to improve functioning on certain tasks without stimulating signals throughout the brain. Kuhar questioned whether “smart drugs” pose unique challenges, compared to other types of drugs. From a pharmacology perspective, he said there is less distinction between therapy and enhancement, compared to a perspective imposed by regulators or insurance companies. He described three basic concerns: safety (avoiding toxicity or unacceptable side effects), freedom (lack of coercion from governments or employers) and fairness.

“Every drug has side effects,” he said. “There has to be a balance between the benefits versus the risks, and regulation plays an important role in that.”

He identified antidepressants and treatments for attention deficit-hyperactivity disorder or the symptoms of Alzheimer’s disease as already raising similar issues. The FDA has designated mild cognitive impairment associated with aging as an open area for pharmaceutical development, he noted.

James Hughes, a sociologist from Trinity College and executive director of the Institute for Ethics and Emerging Technologies, welcomed new technologies that he said could not only treat disease, but also enhance human capabilities and address social challenges such as criminal rehabilitation. However, he did identify potential “Ulysses problems”, where users of new technologies would need to exercise control and judgment.

In contrast, historian and Judaic scholar Hava Tirosh-Samuelson, from Arizona State University, decried an “overly mechanistic and not culturally-based understanding of what it means to be human.” She described transhumanism as a utopian extension of 19th century utilitarianism as expounded by thinkers such as Jeremy Bentham.

“Is the brain simply a computational machine?” she asked.

The use of military metaphors – such as “the war on cancer” – in the context of mental illness creates the false impression that everything is correctable or even perfectable, she said.

Emory neuroscience program director Yoland Smith said he wants ethics to become a strong component of Emory’s neuroscience program, with similar discussions and debates to come in future years.

Posted on by Quinn Eastman in Neuro Leave a comment

The Scientist ranks Emory one of top 15 best places to work for postdocs

This year, the readers of The Scientist magazine have ranked Emory University as the 11th best place to work for postdocs in the United States. Among Emory’s strengths, respondents cited training and mentoring, and career development opportunities.

The top U.S. institution was the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts. The top international institution was University College, London. Emory has previously ranked as high as number 4 (in 2006) in The Scientist’s best places to work for postdocs survey.

The ranking was based on responses from 2,881 nontenured life scientists working in academia, industry or noncommercial research institutions. 76 institutions in the United States and 17 international institutions were included.

Emory employs nearly 700 postdoctoral fellows in laboratories in the School of Medicine, Yerkes National Primate Research Center, Emory College, the Graduate School of Arts and Sciences, Rollins School of Public Health and Nell Hodgson Woodruff School of Nursing.

After receiving their PhD degrees, life sciences graduates launch their research careers by working for several years as postdoctoral fellows in the laboratories of established scientists. In addition to engaging in sometimes grueling laboratory research, many postdocs teach, mentor graduate and undergraduate students and apply for their own funding on a limited basis.

 

Posted on by Quinn Eastman in Uncategorized Leave a comment

New Biological Pathway Identified for PTSD

Emory MedicalHorizon

High blood levels of a hormone produced in response to stress are linked to post-traumatic stress disorder in women but not men, a study from researchers at Emory University and the University of Vermont has found.

The results were published in the Feb. 24 issue of Nature.

The hormone, called PACAP (pituitary adenylate cyclase-activating polypeptide), is known to act throughout the body and the brain, modulating central nervous system activity, metabolism, blood pressure, pain sensitivity and immune function. The identification of PACAP as an indicator of PTSD may lead to new diagnostic tools and eventually, to new treatments for anxiety disorders.


Video on YouTube

“Few biological markers have been available for PTSD or for psychiatric diseases in general,” says first author Kerry Ressler, MD, PhD, associate professor of psychiatry and behavioral sciences at Emory University School of Medicine and a researcher at Yerkes National Primate Research Center. “These results give us a new window into the biology of PTSD.”

Read more @ emoryhealthsciences.org.

Posted on by Wendy Darling in Neuro Leave a comment

One reason why SIV-infected sooty mangabeys can avoid AIDS

Sooty mangabeys are a variety of Old World monkey that can be infected by HIV’s cousin SIV, but do not get AIDS. Emory immunologist and Georgia Research Alliance Eminent Scholar Guido Silvestri, MD, has been a strong advocate for examining non-human primates such as the sooty mangabey, which manage to handle SIV infection without crippling their immune systems. Silvestri is division chief of microbiology and immunology at Yerkes National Primate Research Center.

Research shows sooty mangabeys have T cells that can do the same job as those targeted by SIV, even if they don't have the same molecules on their surfaces

A recent paper in the Journal of Clinical Investigation reveals that sooty mangabeys have T cells that perform the same functions as those targeted by SIV and HIV, but have different clothing.

Silvestri and James Else, the animal resources division chief at Yerkes, are co-authors on the paper, while Donald Sodora at Seattle Biomedical Research Institute is senior author.

One main target for SIV and HIV is the group of T cells with the molecule CD4 on their surfaces. These are the “helper” T cells that keep the immune system humming. Doctors treating people with HIV infections tend to keep an eye on their CD4 T cell counts.

In the paper, the scientists show that sooty mangabeys infected with SIV lose their CD4 T cells, without losing the ability to regulate their immune systems. What’s remarkable here is that sooty mangabeys appear to have “double negative” or DN T cells that can perform the same functions as those lost to SIV infection, even though they don’t have CD4.

CD4 isn’t just decoration for T cells. It’s a part of how they recognize bits of host or pathogen protein in the context of MHC class II (the molecule that “presents” the bits on the outside of target cells). Somehow, the T cells in sooty mangabeys have a way to get around this requirement and still regulate the immune system competently. How they do this is the topic of ongoing research.

The authors write:

It will be important to assess DN T cells in HIV-infected patients, particularly to determine whether these cells are preserved and functional in long-term nonprogressors. These efforts may lead to future immune therapies or vaccine modalities designed to modulate DN T cell function. Indeed, the main lesson we have learned to date from this cohort of SIV-infected CD4-low mangabeys may be that managing immune activation and bolstering the function of nontarget T cells through better vaccines and therapeutics has the potential to contribute to preserved immune function and a nonprogressive outcome in HIV infection even when CD4+ T cell levels become low.

Posted on by Quinn Eastman in Immunology Leave a comment

Brain chemical linked to migraines could be anxiety target

Neuroscientist Michael Davis, PhD, and his colleagues have devoted years to mapping out the parts of the brain responsible for driving fear and anxiety. In a recent review article, they describe the differences between fear and anxiety in this way:

Fear is a generally adaptive state of apprehension that begins rapidly and dissipates quickly once the threat is removed (phasic fear). Anxiety is elicited by less specific and less predictable threats, or by those that are physically or psychologically more distant (sustained fear).

Michael Davis is an investigator at Yerkes National Primate Research Center and Emory School of Medicine

A host of their studies suggest that one part of the brain, the amygdala, is instrumental in producing “phasic fear,” while the bed nucleus of the stria terminalis (BNST) is important for “sustained fear.”

In a new report in the Journal of Neuroscience, Davis’ team describes the effects of a brain communication chemical, which is known primarily for its role in driving migraine headaches, in enhancing anxiety.

“This is the first study to show a role of this peptide, in a brain area we’ve identified as being important for anxiety.  This could lead to new drug targets to selectively reduce anxiety,” Davis says.

His team found that introducing calcitonin gene-related peptide (CGRP) into rats’ BNSTs can increase the anxiety they experience from loud noises or light, in that they startle more and avoid well-lit places. This peptide appears to activate other parts of the brain including the amygdala, hypothalamus and brainstem, producing fear-related symptoms.

Slice of rat brain showing the bed nucleus of the stria terminalis (BNST) and the central amygdala (Ce)

If Davis and his colleagues block CGRP’s function by introducing a short, decoy version of CGRP into the BNST, the reverse does not happen: the rats are not more relaxed. However, the short version does block the startle-enhancing effects of a smelly chemical produced by foxes that scientists use to heighten anxiety-like behavior in rats. This suggests that interfering with CGRP can reduce fear-related symptoms in situations where the rats are already under stress.

“Blockade of CGRP receptors may thus represent a novel therapeutic target for the treatment of stress-induced anxiety and related psychopathologies such as post-traumatic stress disorder,” says the paper’s first author, postdoctoral fellow Kelly Sink.

In fact, experimental drugs that work against CGRP are already in clinical trials to treat migraine headaches. But first, Sink reports that she and her colleagues are examining the relationship between CGRP and the stress hormone CRF (corticotropin-releasing factor) — another target of pharmacological interest — in the parts of the brain important for fear responses.

Posted on by Quinn Eastman in Neuro 1 Comment

National Academy of Sciences recognizes Yerkes Primate Center neuroscientist

Elizabeth A. Buffalo, PhD

The National Academy of Sciences (NAS) has recognized 13 individuals with awards acknowledging extraordinary scientific achievements in the areas of biology, chemistry, physics, economics and psychology.

Elizabeth A. Buffalo, PhD, a researcher at the Yerkes National Primate Research Center, is one of two recipients of the Troland Research Awards. Buffalo is being honored for innovative, multidisciplinary study of the hippocampus and the neural basis of memory. Troland Research Awards of $50,000 are given annually to recognize unusual achievement by young investigators and to further empirical research in experimental psychology.

The recipients will be honored in a ceremony on Sunday, May 1, during the NAS 148th annual meeting.

Posted on by Holly Korschun in Neuro Leave a comment
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