Creative Minds: Potential Diabetes Lessons from Binge-Eating Snakes

Secor with a snake

Stephen Secor/Credit: Secor Lab

Many people would do just about anything to avoid an encounter with a snake. Not Stephen Secor. Growing up in central New York State, Secor was drawn to them. He’d spend hours frolicking through forest and field, flipping rocks and hoping to find one. His animal-loving mother encouraged him to keep looking, and she even let him keep a terrarium full of garter snakes in his bedroom. Their agreement: He must take good care of them—and please make sure they don’t get loose.

As a teen, Secor considered a career as a large-animal veterinarian. But a college zoology course led him right back to his fascination with snakes. Now a professor at the University of Alabama, Tuscaloosa, he’s spent 25 years trying to understand how some snakes, such as the Burmese python shown above, can fast for weeks or even months, and then go on a sudden food binge. Secor’s interest in the feast-or-famine digestive abilities of these snakes has now taken an unexpected turn that he never saw coming: a potential treatment to help people with diabetes.

Continue reading

Snapshots of Life: Healing Spinal Cord Injuries

Nerve cell on a nanofiber gel

Credit: Mark McClendon, Zaida Alvarez Pinto, Samuel I. Stupp, Northwestern University, Evanston, IL

When someone suffers a fully severed spinal cord, it’s considered highly unlikely the injury will heal on its own. That’s because the spinal cord’s neural tissue is notorious for its inability to bridge large gaps and reconnect in ways that restore vital functions. But the image above is a hopeful sight that one day that could change.

Here, a mouse neural stem cell  (blue and green) sits in a lab dish, atop a special gel containing a mat of synthetic nanofibers (purple). The cell is growing and sending out spindly appendages, called axons (green), in an attempt to re-establish connections with other nearby nerve cells.

Continue reading

Regenerative Medicine: New Clue from Fish about Healing Spinal Cord Injuries

Zebrafish Spinal Cord

Caption: Tissue section of zebrafish spinal cord regenerating after injury. Glial cells (red) cross the gap between the severed ends first. Neuronal cells (green) soon follow. Cell nuclei are stained blue and purple.
Credit: Mayssa Mokalled and Kenneth Poss, Duke University, Durham, NC

Certain organisms have remarkable abilities to achieve self-healing, and a fascinating example is the zebrafish (Danio rerio), a species of tropical freshwater fish that’s an increasingly popular model organism for biological research. When the fish’s spinal cord is severed, something remarkable happens that doesn’t occur in humans: supportive cells in the nervous system bridge the gap, allowing new nerve tissue to restore the spinal cord to full function within weeks.

Pretty incredible, but how does this occur? NIH-funded researchers have just found an important clue. They’ve discovered that the zebrafish’s damaged cells secrete a molecule known as connective tissue growth factor a (CTGFa) that is essential in regenerating its severed spinal cord. What’s particularly encouraging to those looking for ways to help the 12,000 Americans who suffer spinal cord injuries each year is that humans also produce a form of CTGF. In fact, the researchers found that applying human CTGF near the injured site even accelerated the regenerative process in zebrafish. While this growth factor by itself is unlikely to produce significant spinal cord regeneration in human patients, the findings do offer a promising lead for researchers pursuing the next generation of regenerative therapies.

Continue reading

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

Creative Minds: Can Salamanders Show Us How to Regrow Limbs?

Jessica Whited

Jessica Whited /Credit: LightChaser Photography

Jessica Whited enjoys spending time with her 6-year-old twin boys, reading them stories, and letting their imaginations roam. One thing Whited doesn’t need to feed their curiosity about, however, is salamanders—they hear about those from Mom almost every day. Whited already has about 1,000 rare axolotl salamanders in her lab at Harvard University and Brigham and Women’s Hospital, Cambridge, MA. But caring for the 9-inch amphibians, which originate from the lakes and canals underlying Mexico City, certainly isn’t child’s play. Axolotls are entirely aquatic–their name translates to “water monster”; they like to bite each other; and they take 9 months to reach adulthood.

Like many other species of salamander, the axolotl (Ambystoma mexicanum) possesses a remarkable, almost magical, ability to grow back lost or damaged limbs. Whited’s interest in this power of limb regeneration earned her a 2015 NIH Director’s New Innovator Award. Her goal is to discover how the limbs of these salamanders know exactly where they’ve been injured and start regrowing from precisely that point, while at the same time forging vital new nerve connections to the brain. Ultimately, she hopes her work will help develop strategies to explore the possibility of “awakening” this regenerative ability in humans with injured or severed limbs.

Continue reading