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

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.

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Snapshots of Life: Neurons in a New Light

Mouse Midbrain

Credit: Michael Shribak, Marine Biological Laboratory, Woods Hole, MA

Birds do it, bees do it, and even educated fleas do it. No, not fall in love, as the late Ella Fitzgerald so famously sang. Birds and insects can see polarized light—that is, light waves transmitted in a single directional plane—in ways that provides them with a far more colorful and detailed view of the world than is possible with the human eye.

Still, thanks to innovations in microscope technology, scientists have been able to tap into the power of polarized light vision to explore the inner workings of many complex biological systems, including the brain. In this image, researchers used a recently developed polarized light microscope to trace the spatial orientation of neurons in a thin section of the mouse midbrain. Neurons that stretch horizontally appear green, while those oriented at a 45-degree angle are pinkish-red and those at 225 degrees are purplish-blue. What’s amazing is that these colors don’t involve staining or tagging the cells with fluorescent markers: the colors are generated strictly from the light interacting with the physical orientation of each neuron.

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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.

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Cool Videos: Flashes of Neuronal Brilliance

When you have a bright idea or suddenly understand something, you might say that a light bulb just went on in your head. But, as the flashing lights of this very cool video show, the brain’s signaling cells, called neurons, continually switch on and off in response to a wide range of factors, simple or sublime.

The technology used to produce this video—a recent winner in the Federation of American Societies for Experimental Biology’s BioArt contest—takes advantage of the fact that whenever a neuron is activated, levels of calcium increase inside the cell. To capture that activity, graduate student Caitlin Vander Weele in Kay M. Tye’s lab at the Picower Institute for Learning and Memory, Massachusetts Institute of Technology (MIT), Cambridge, MA, engineered neurons in a mouse’s brain to produce a bright fluorescent signal whenever calcium increases. Consequently, each time a neuron was activated, the fluorescent indicator lit up and the changes were detected with a miniature microscope. The brighter the flash, the greater the activity!

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Rare Disease Mystery: Nodding Syndrome May Be Linked to Parasitic Worm

Rural Uganda village gathering

Caption: Village in the East Africa nation of Uganda
Credit: Centers for Disease Control and Prevention

In the early 1960s, reports began to surface that some children living in remote villages in East Africa were suffering mysterious episodes of “head nodding.” The condition, now named nodding syndrome, is recognized as a rare and devastating form of epilepsy. There were hints that the syndrome might be caused by a parasitic worm called Onchocerca volvulus, which is transmitted through the bites of blackflies. But no one had been able to tie the parasitic infection directly to the nodding heads.

Now, NIH researchers and their international colleagues think they’ve found the missing link. The human immune system turns out to be a central player. After analyzing blood and cerebrospinal fluid of kids with nodding syndrome, they detected a particular antibody at unusually high levels [1]. Further studies suggest the immune system ramps up production of that antibody to fight off the parasite. The trouble is those antibodies also react against a protein in healthy brain tissue, apparently leading to progressive cognitive dysfunction, neurological deterioration, head nodding, and potentially life-threatening seizures.

The findings, published in Science Translational Medicine, have important implications for the treatment and prevention of not only nodding syndrome, but perhaps other autoimmune-related forms of epilepsy. As people in the United States and around the globe today observe the 10th anniversary of international Rare Disease Day, this work provides yet another example of how rare disease research can shed light on more common diseases and fundamental aspects of human biology.

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