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Measuring Brain Chemistry

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Anne Andrews

Anne Andrews
Credit: From the American Chemical Society’s “Personal Stories of Discovery”

Serotonin is one of the chemical messengers that nerve cells in the brain use to communicate. Modifying serotonin levels is one way that antidepressant and anti-anxiety medications are thought to work and help people feel better. But the precise nature of serotonin’s role in the brain is largely unknown.

That’s why Anne Andrews set out in the mid-1990s as a fellow at NIH’s National Institute of Mental Health to explore changes in serotonin levels in the brains of anxious mice. But she quickly realized it wasn’t possible. The tools available for measuring serotonin—and most other neurochemicals in the brain—couldn’t offer the needed precision to conduct her studies.

Instead of giving up, Andrews did something about it. In the late 1990s, she began formulating an idea for a neural probe to make direct and precise measurements of brain chemistry. Her progress was initially slow, partly because the probe she envisioned was technologically ahead of its time. Now at the University of California, Los Angeles (UCLA) more than 15 years later, she’s nearly there. Buoyed by recent scientific breakthroughs, the right team to get the job done, and the support of a 2017 NIH Director’s Transformative Research Award, Andrews expects to have the first fully functional devices ready within the next two years.


Creative Minds: Seeing Memories in a New Light

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Steve Ramirez

Steve Ramirez/Joshua Sariñana

Whether it’s lacing up for a morning run, eating blueberry scones, or cheering on the New England Patriots, Steve Ramirez loves life and just about everything in it. As an undergraduate at Boston University, this joie de vivre actually made Ramirez anxious about choosing just one major. A serendipitous conversation helped him realize that all of the amazing man-made stuff in our world has a common source: the human brain.

So, Ramirez decided to pursue neuroscience and began exploring the nature of memory. Employing optogenetics (using light to control brain cells) in mice, he tagged specific neurons that housed fear-inducing memories, making the neurons light sensitive and amenable to being switched on at will.

In groundbreaking studies that earned him a spot in Forbes 2015 “30 Under 30” list, Ramirez showed that it’s possible to reactivate memories experimentally in a new context, recasting them in either a more negative or positive behavior-changing light [1–3]. Now, with support from a 2016 NIH Director’s Early Independence Award, Ramirez, who runs his own lab at Boston University, will explore whether activating good memories holds promise for alleviating chronic stress and psychiatric disease.


Creative Minds: A Transcriptional “Periodic Table” of Human Neurons

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neuronal cell

Caption: Mouse fibroblasts converted into induced neuronal cells, showing neuronal appendages (red), nuclei (blue) and the neural protein tau (yellow).
Credit: Kristin Baldwin, Scripps Research Institute, La Jolla, CA

Writers have The Elements of Style, chemists have the periodic table, and biomedical researchers could soon have a comprehensive reference on how to make neurons in a dish. Kristin Baldwin of the Scripps Research Institute, La Jolla, CA, has received a 2016 NIH Director’s Pioneer Award to begin drafting an online resource that will provide other researchers the information they need to reprogram mature human skin cells reproducibly into a variety of neurons that closely resemble those found in the brain and nervous system.

These lab-grown neurons could be used to improve our understanding of basic human biology and to develop better models for studying Alzheimer’s disease, autism, and a wide range of other neurological conditions. Such questions have been extremely difficult to explore in mice and other animal models because they have shorter lifespans and different brain structures than humans.


Creative Minds: Helping More Kids Beat Anxiety Disorders

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Dylan Gee

Dylan Gee

While earning her Ph.D. in clinical psychology, Dylan Gee often encountered children and adolescents battling phobias, panic attacks, and other anxiety disorders. Most overcame them with the help of psychotherapy. But not all of the kids did, and Gee spent many an hour brainstorming about how to help her tougher cases, often to find that nothing worked.

What Gee noticed was that so many of the interventions she pondered were based on studies in adults. Little was actually known about the dramatic changes that a child’s developing brain undergoes and their implications for coping under stress. Gee, an assistant professor at Yale University, New Haven, CT, decided to dedicate her research career to bridging the gap between basic neuroscience and clinical interventions to treat children and adolescents with persistent anxiety and stress-related disorders.


LabTV: Curious About Fatigue Related to Cancer Therapy

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Leorey Saligan

As this LabTV profile of an outstanding nurse-scientist shows, there are many different paths to a career in biomedical research. Leorey Saligan grew up in the Philippines, where the challenges and rewards of caring for sick family members inspired him to become a nurse. His first job was at a nursing home in Midland, TX, and the next at a nearby hospital. Later, Saligan moved to Norfolk, VA, where as a nurse practitioner he began caring for people with sarcoidosis, an inflammatory disease that affects several organ systems.

Saligan went on to pursue a Ph.D. in nursing at Virginia’s Hampton University, writing his dissertation on the chronic vision problems associated with sarcoidosis. To gather more data on such problems, he joined NIH’s National Institute of Nursing Research in Bethesda, MD, and, with the help of colleagues, carried out a clinical study. To Saligan’s surprise, the data showed that fatigue, rather than poor vision, was the top concern of people with sarcoidosis. That discovery sparked his research interest in fatigue—an interest now focused on the intense, often debilitating fatigue that many people with cancer experience both during and after treatment, particularly radiation therapy.

Like people with sarcoidosis, people undergoing cancer treatment report that fatigue is the symptom that most negatively affects their quality of life. Many find the fatigue so distressing that their treatment regimens have to be reduced or even halted—actions that may have a negative effect on the cancer-killing power of such treatments. And, for some folks, the fatigue can be long lasting, persisting for months or even years after cancer therapy ends.

By analyzing blood and tissue samples donated by volunteers who are undergoing or who have undergone cancer treatments, Saligan and colleagues from NIH’s Clinical Center and National Cancer Institute have uncovered several promising leads in their effort to gain a better understanding of the molecular mechanisms of treatment-related fatigue. He is also working with behavioral researchers to explore the relationship of fatigue with pain, depression, anxiety, sleep disturbances, and other symptoms. Ultimately, this NIH tenure-track investigator (who also happens to be an officer in the U.S. Public Health Service) wants to see this scientific knowledge translated into effective ways of treating or preventing the fatigue that is a most unfortunate side effect of potentially life-saving cancer therapies.

Links:

LabTV

Leorey N. Saligan (National Institute of Nursing Research/NIH)

Investigating Molecular-Genetic Correlates of Fatigue Experienced by Cancer Patients Receiving Treatment (ClinicalTrials.gov/NIH)

Effect of Ketamine on Fatigue Following Cancer Therapy (ClinicalTrials.gov/NIH)

Science Careers (National Institute of General Medical Sciences/NIH)

Careers Blog (Office of Intramural Training/NIH)

Scientific Careers at NIH

 


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