Creative Minds: Reprogramming the Brain

Cells of a mouse retina

Caption: Neuronal circuits in the mouse retina. Cone photoreceptors (red) enable color vision; bipolar neurons (magenta) relay information further along the circuit; and a subtype of bipolar neuron (green) helps process signals sensed by other photoreceptors in dim light.
Credit: Brian Liu and Melanie Samuel, Baylor College of Medicine, Houston.

When most people think of reprogramming something, they probably think of writing code for a computer or typing commands into their smartphone. Melanie Samuel thinks of brain circuits, the networks of interconnected neurons that allow different parts of the brain to work together in processing information.

Samuel, a researcher at Baylor College of Medicine, Houston, wants to learn to reprogram the connections, or synapses, of brain circuits that function less well in aging and disease and limit our memory and ability to learn. She has received a 2016 NIH Director’s New Innovator Award to decipher the molecular cues that encourage the repair of damaged synapses or enable neurons to form new connections with other neurons. Because extensive synapse loss is central to most degenerative brain diseases, Samuel’s reprogramming efforts could help point the way to preventing or correcting wiring defects before they advance to serious and potentially irreversible cognitive problems.

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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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Snapshots of Life: Development in Exquisite Detail

Developmental biology

Credit: Shachi Bhatt and Paul Trainor, Stowers Institute for Medical Research, Kansas City, MO

If you’ve ever tried to take photos of wiggly kids, you know that it usually takes several attempts before you get the perfect shot. It’s often the same for biomedical researchers when taking images with microscopes because there are so many variables—from sample preparation to instrument calibration—to take into account. Still, there are always exceptions where everything comes together just right, and you are looking at one of them! On her first try at using a confocal microscope to image this cross-section of a mouse embryo’s torso, postdoc Shachi Bhatt captured a gem of an image that sheds new light on mammalian development.

Bhatt, who works in the NIH-supported lab of Paul Trainor at the Stowers Institute for Medical Research, Kansas City, MO, produced this micrograph as part of a quest to understand the striking parallels seen between the development of the nervous system and the vascular system in mammals. Fluorescent markers were used to label proteins uniquely expressed in each type of tissue: reddish-orange delineates developing nerve cells; gray highlights developing blood vessels; and yellow shows where the nerve cells and blood vessels overlap.

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