Warren symposium follows legacy of geneticist giant

If we want to understand how the brain creates memories, and how genetic disorders distort the brain’s machinery, then the fragile X gene is an ideal place to start. That’s why the Stephen T. Warren Memorial Symposium, taking place November 28-29 at Emory, will be a significant event for those interested in neuroscience and genetics. Stephen T. Warren, 1953-2021 Warren, the founding chair of Emory’s Department of Human Genetics, led an international team that discovered Read more

Mutations in V-ATPase proton pump implicated in epilepsy syndrome

Why and how disrupting V-ATPase function leads to epilepsy, researchers are just starting to figure Read more

Tracing the start of COVID-19 in GA

At a time when COVID-19 appears to be receding in much of Georgia, it’s worth revisiting the start of the pandemic in early 2020. Emory virologist Anne Piantadosi and colleagues have a paper in Viral Evolution on the earliest SARS-CoV-2 genetic sequences detected in Georgia. Analyzing relationships between those virus sequences and samples from other states and countries can give us an idea about where the first COVID-19 infections in Georgia came from. We can draw Read more

Michael Davis

Making cardiac progenitor cells feel at home

One lab uses goopy alginate, another uses peptides that self-assemble into hydrogels. The objective is the same: protecting cells that are injected into the heart and making them feel like they’re at home.

Around the world, thousands of heart disease patients have been treated in clinical studies with some kind of cell-based therapy aimed at regenerating the heart muscle or at least promoting its healing. This approach is widely considered promising, but its effectiveness is limited in that most of the cells don’t stay in the heart or die soon after being introduced. [UPDATE: Nice overview of cardiac cell therapy controversy in July 18 Science]

Biomedical engineer Mike Davis and his colleagues recently published a paper in Biomaterials describing hydrogels that can encourage cardiac progenitor cells injected into the heart to stay in place. The first author is former graduate student Archana Boopathy, who recently started her postdoctoral work at MIT. Davis has been working with these self-assembling peptides for some time: see this 2005 Circulation paper he published during his own postdoctoral work with Richard Lee at Harvard.DavisDiagram

How do these hydrogels keep cells from washing away? We don’t have to go much beyond the name: think Jello. Researchers design snippets of proteins (peptides) that, like Jello*, form semisolid gels under the right conditions in solution. Helpfully, they also are customized with molecular tools for making cardiac progenitor cells happy. Read more

Posted on by Quinn Eastman in Heart 1 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. Individuals who constantly suffer from anxiety attacks and other mental health issues may need to consult with an anxiety psychiatrist for proper diagnosis and treatments for anxiety. Licensed therapists administer ketamine assisted psychotherapy to treat resistant depression in controlled settings.

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“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 Leave a comment