Snapshots of Life: Wired for Nerve Regeneration

Nerve cells

Credit: Laura Struzyna, Cullen Laboratory, Perelman School of Medicine, University of Pennsylvania, Philadelphia

Getting nerve cells to grow in the lab can be a challenge. But when it works, the result can be a thing of beauty for both science and art. What you see growing in the Petri dish shown above are nerve cells from an embryonic rat. On the bottom left is a dorsal root ganglion (dark purple), which is a cluster of sensory nerve bodies normally found just outside the spinal cord. To the right are the nuclei (light purple) and axons (green) of motor neurons, which are the nerve cells involved in forming key signaling networks.

Laura Struzyna, a graduate student in the lab of NIH grantee D. Kacy Cullen at the University of Pennsylvania’s Perelman School of Medicine, Philadelphia, is using laboratory-grown nerve cells in her efforts to learn how to bioengineer nerve grafts. The hope is this work will one day lead to grafts that can be used to treat people whose nerves have been damaged by car accidents or other traumatic injuries.

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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.

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Fighting Depression: Ketamine Metabolite May Offer Benefits Without the Risks

Depressed Woman

Thinkstock/Ryan McVay

For people struggling with severe depression, antidepressants have the potential to provide much-needed relief, but they often take weeks to work. That’s why there is growing excitement about reports that the anesthetic drug ketamine, when delivered intravenously in very low doses, can lift depression and suicidal thoughts within a matter of hours. Still, there has been reluctance to consider ketamine for widespread treatment of depression because, even at low doses, it can produce very distressing side effects, such as dissociation—a sense of disconnection from one’s own thoughts, feelings, and sense of identity. Now, new findings suggest there may be a way to tap into ketamine’s depression-fighting benefits without the side effects.

In a mouse study published in the journal Nature, an NIH-funded research team found that the antidepressant effects of ketamine are produced not by the drug itself, but by one of its metabolites—a substance formed as the body breaks ketamine down. What’s more, the work demonstrates that this beneficial metabolite does not cause the risky dissociation effects associated with ketamine. While further development and subsequent clinical trials are needed, the findings are a promising step toward the development of a new generation of rapid-acting antidepressant drugs.

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Cool Videos: Reconstructing the Cerebral Cortex

Click for video
This colorful cylinder could pass for some sort of modern art sculpture, but it actually represents a sneak peak at some of the remarkable science that we can look forward to seeing from the Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative. In a recent study in the journal Cell [1], NIH grantee Jeff Lichtman of Harvard University, Cambridge, MA and his colleagues unveiled the first digitized reconstruction of tissue from the mammalian cerebral cortex—the outermost part of the brain, responsible for complex behaviors.

Specifically, Lichtman’s group mapped in exquisite detail a very small cube of a mouse’s cerebral cortex. In fact, the cube is so tiny (smaller than a grain of sand!) that it contained no whole cells, just a profoundly complex tangle of finger-like nerve cell extensions called axons and dendrites. And what you see in this video is just one cylindrical portion of that tissue sample, in which Licthtman and colleagues went full force to identify and label every single cellular and intracellular element. The message-sending axons are delineated in an array of pastel colors, while more vivid hues of red, green, and purple mark the message-receiving dendrites and bright yellow indicates the nerve-insulating glia. In total, the cylinder contains parts of about 600 axons, 40 different dendrites, and 500 synapses, where nerve impulses are transmitted between cells.

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Snapshots of Life: A Colorful Look Inside the Retina

Mapping neurons in the retina

Credit: Amy Robinson, Alex Norton, William Silversmith, Jinseop Kim, Kisuk Lee, Aleks Zlasteski, Matt Green, Matthew Balkam, Rachel Prentki, Marissa Sorek, Celia David, Devon Jones, and Doug Bland, Massachusetts Institute of Technology, Cambridge, MA; Sebastian Seung, Princeton University, Princeton, NJ

This eerie scene might bring back memories of the computer-generated alien war machines from Steven Spielberg’s War of the Worlds thriller. But what you’re seeing is a computer-generated depiction of a quite different world—the world inside the retina, the light-sensitive tissue that lines the back of the eye. The stilt-legged “creatures” are actually ganglion nerve cells, and what appears to be their long “noses” are fibers that will eventually converge to form the optic nerve that relays visual signals to the brain. The dense, multi-colored mat near the bottom of the image is a region where the ganglia and other types of retinal cells interact to convey visual information.

What I find particularly interesting about this image is that it was produced through the joint efforts of people who played EyeWire, an internet crowdsourcing game developed in the lab of computational neuroscientist Sebastian Seung, now at Princeton University in New Jersey.  Seung and his colleagues created EyeWire using a series of high-resolution microscopic images of the mouse retina, which were digitized into 3D cubes containing dense skeins of branching nerve fibers. It’s at this point where the crowdsourcing came in. Online gamers—most of whom aren’t scientists— volunteered for a challenge that involved mapping the 3D structure of individual nerve cells within these 3D cubes. Players literally colored-in the interiors of the cells and progressively traced their long extensions across the image to distinguish them from their neighbors. Sounds easy, but the branches are exceedingly thin and difficult to follow.

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