Cool Videos: Regenerating Nerve Fibers

If you enjoy action movies, you can probably think of a superhero—maybe Wolverine?—who can lose a limb in battle, yet grow it right back and keep on going. But could regenerating a lost limb ever happen in real life? Some scientists are working hard to understand how other organisms do this.

As shown in this video of a regenerating fish fin, biology can sometimes be stranger than fiction. The zebrafish (Danio rerio), which is a species of tropical freshwater fish that’s an increasingly popular model organism for biological research, is among the few vertebrates that can regrow body parts after they’ve been badly damaged or even lost. Using time-lapse photography over a period of about 12 hours, NIH grantee Sandra Rieger, now at MDI Biological Laboratory, Bar Harbor, ME, used a fluorescent marker (green) to track a nerve fiber spreading through the skin of a zebrafish tail fin (gray). The nerve regeneration was occurring in tissue being spontaneously formed to replace a section of a young zebrafish’s tail fin that had been lopped off 3 days earlier.

Along with other tools, Rieger is using such imaging to explore how the processes of nerve regeneration and wound healing are coordinated. The researcher started out by using a laser to sever nerves in a zebrafish’s original tail fin, assuming that the nerves would regenerate—but they did not! So, she went back to the drawing board and discovered that if she also used the laser to damage some skin cells in the tail fin, the nerves regenerated. Rieger suspects the answer to the differing outcomes lies in the fact that the fish’s damaged skin cells release hydrogen peroxide, which may serve as a critical prompt for the regenerative process [1]. Rieger and colleagues went on discover that the opposite is also true: when they used a cancer chemotherapy drug to damage skin cells in a zebrafish tail fin, it contributed to the degeneration of the fin’s nerve fibers [2].

Based on these findings, Rieger wants to see whether similar processes may be going on in the hands and feet of cancer patients who struggle with painful nerve damage, called peripheral neuropathy, caused by certain chemotherapy drugs, including taxanes and platinum compounds. For some people, the pain and tingling can be so severe that doctors must postpone or even halt cancer treatment. Rieger is currently working with a collaborator to see if two protective molecules found in the zebrafish might be used to reduce or prevent chemotherapy-induced peripheral neuropathy in humans.

In recent years, a great deal of regenerative medicine has focused on learning to use stem cell technologies to make different kinds of replacement tissue. Still, as Rieger’s work demonstrates, there remains much to be gained from studying model organisms, such as the zebrafish and axolotl salamander, that possess the natural ability to regenerate limbs, tissues, and even internal organs. Now, that’s a super power we’d all like to have.

Reference:

[1] Hydrogen peroxide promotes injury-induced peripheral sensory axon regeneration in the zebrafish skin. Rieger S, Sagasti A. PLoS Biol. 2011 May;9(5):e1000621

[2] Paclitaxel-induced epithelial damage and ectopic MMP-13 expression promotes neurotoxicity in zebrafish. Lisse TS, Middleton LJ, Pellegrini AD, Martin PB, Spaulding EL, Lopes O, Brochu EA, Carter EV, Waldron A, Rieger S. Proc Natl Acad Sci U S A. 2016 Apr 12;113(15):E2189-E2198.

Links:

Chemotherapy-Induced Peripheral Neuropathy (National Cancer Institute/NIH)

Learning About Human Biology From a Fish (National Institute of General Medical Sciences/NIH)

Sandra Rieger (MDI Biological Laboratory, Bar Harbor, ME)

NIH Support: National Institute of Dental and Craniofacial Research; National Institute of General Medical Sciences; National Institute of Neurological Disorders and Stroke

LabTV: Curious About Fatigue Related to Cancer Therapy

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