Stories about: neurobiology

Novel therapeutic cocktail could restore fine motor skills after spinal cord injury and stroke

CST axons sprout from intact to injured side
Therapeutic mixture induces sprouting of axons from healthy (L) into the injured (R) side of the spinal cord.

Neuron cells have long finger-like structures, called axons, that extend outward to conduct impulses and transmit information to other neurons and muscle fibers. After spinal cord injury or stroke, axons originating in the brain’s cortex and along the spinal cord become damaged, disrupting motor skills. Now, reported today in Neuron, a team of scientists at Boston Children’s Hospital has developed a method to promote axon regrowth after injury.

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A calmer rodent is a better rodent for pain medication research

The global market for pain medications is huge — some estimates predict it will hit $41.6 billion by 2017. However, the costs of pain medicine development are huge, too; it takes roughly $900 million to bring a new analgesic compound to market. In part, this is because some 80 percent of compounds that look promising in preclinical animal studies (largely in rodents) fail in late-stage clinical trials.

David Roberson, MBA, a neuroscience graduate student in the F.M. Kirby Neurobiology Center at Boston Children’s Hospital, wants to make those preclinical studies better at predicting whether a new compound will work safely in people — by studying rodents at “home.”

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Breaking the allergic asthma cycle…by targeting nerve endings

asthma therapeuticsExisting asthma medications work by suppressing inflammatory signaling by immune cells or by dilating constricted airways. Over time, though, these drugs’ benefits can wane. New research supports a surprising new tactic for controlling asthma: targeting sensory nerve endings in the lungs with a selective drug.

Our lungs are known to contain specialized sensory neurons known as nociceptors that connect to the brainstem. Best known for causing the perception of pain, nocieptors also trigger the cough reflex in the lungs when they detect potential harms like dust particles, chemical irritants or allergens. Nociceptor nerve endings are known to be more plentiful and more readily activated in people with asthma. Now it’s also clear that they help drive allergic inflammation.

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On the clock: Circadian genes may regulate brain plasticity

brain circadian rhythmsFirst in a two-part series on circadian biology and disease. Read part 2.

It’s long been known that a master clock in the hypothalamus, deep in the center of our brain, governs our bodily functions on a 24-hour cycle. It keeps time through the oscillatory activity of timekeeper molecules, much of which is controlled by a gene fittingly named Clock.

It’s also been known that the timekeeper molecules and their regulators live outside this master clock, but what exactly they do there remains mysterious. A new study reveals one surprising function: they appear to regulate the timing of brain plasticity—the ability of the brain to learn from and change in response to experiences.

“We found that a cell-intrinsic Clock may control the normal trajectory of brain development,” says Takao Hensch, PhD, a professor in the Departments of Molecular and Cellular Biology and Neurology at Harvard University and a member of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital.

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New Human Neuron Core to analyze ‘disease in a dish’

Human Neuron CoreLast week was a good week for neuroscience. Boston Children’s Hospital received nearly $2.2 million from the Massachusetts Life Sciences Center (MLSC) to create a Human Neuron Core. The facility will allow researchers at Boston Children’s and beyond to study neurodevelopmental, psychiatric and neurological disorders directly in living, functioning neurons made from patients with these disorders.

“Nobody’s tried to make human neurons available in a core facility like this before,” says Robin Kleiman, PhD, Director of Preclinical Research for Boston Children’s Translational Neuroscience Center (TNC), who will oversee the Core along with neurologist and TNC director Mustafa Sahin, MD, PhD, and Clifford Woolf, PhD, of Boston Children’s F.M. Kirby Neurobiology Center. “Neurons are really complicated, and there are many different subtypes. Coming up with standard operating procedures for making each type of neuron reproducibly is labor-intensive and expensive.”

Patient-derived neurons are ideal for modeling disease and for preclinical screening of potential drug candidates, including existing, FDA-approved drugs. Created from induced pluripotent stem cells (iPSCs) made from a small skin sample, the lab-created human neurons capture disease physiology at the cellular level in a way that neurons from rats or mice cannot.

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Modeling pain in a dish: Nociceptors made from skin recreate pain physiology

Pain in a dish nociceptors

Chronic pain, affecting tens of millions of Americans alone, is debilitating and demoralizing. It has many causes, and in the worst cases, people become “hypersensitized”—their nervous systems fire off pain signals in response to very minor triggers.

There are no good medications to calm these signals, in part because the subjectivity of pain makes it difficult to study, and in part because there haven’t been good research models. Drugs have been tested in animal models and “off the shelf” cell lines, some of them engineered to carry target molecules (such as the ion channels that trigger pain signals). Drug candidates emerging from these studies initially looked promising but haven’t panned out in clinical testing.

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The 98%: Proteomics reveals proteins made from ‘noncoding’ DNA

proteins and peptides from noncoding DNA
Probing the genome's 'dark side' could change our view of biology.
Vast chunks of our DNA—fully 98 percent of our genome—are considered “non-coding,” meaning that they’re not thought to carry instructions to make proteins. Yet we already know that this “junk DNA” isn’t completely filler. For example, some sequences are known to code for bits of RNA that act as switches, turning genes on and off.

New research led by Judith Steen, PhD, and Gabriel Kreiman PhD, of Boston Children’s Hospital’s Proteomics Center and Neurobiology program, goes much further in mapping this “dark side” of the genome.

In a report published last month in Nature Communications, they describe a variety of proteins and peptides (smaller chains of amino acids) arising from presumed non-coding DNA sequences. Since they looked in just one type of cell—neurons—these molecules may only be the tip of a large, unexplored iceberg and could change our understanding of biology and disease.

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How things work: Scientists find cellular channels vital for hearing

A mechanosensory hair bundle in the cochlea. Each sensory cell, of which the human ear has about 16,000, has tiny hairs tipped with TMC1 and TMC2 proteins. When sound vibrations strike the bundle, it wiggles back and forth, opening and closing the TMC channels. When open, the channel allows calcium into the cell, initiating an electrical signal to the brain relayed by the 8th cranial nerve. (Image: Yoshiyuki Kawashima)
A mechanosensory hair bundle in the cochlea. Each sensory cell, of which the human ear has about 16,000, has tiny hairs tipped with TMC1 and TMC2 proteins. When sound vibrations strike the bundle, it wiggles back and forth, opening and closing the TMC channels. When open, the channel allows calcium into the cell, initiating an electrical signal to the brain relayed by the 8th cranial nerve. (Image: Yoshiyuki Kawashima)
Ending a 30-year search by scientists, researchers have identified two proteins in the inner ear that are critical for hearing, which, when damaged by genetic mutations, cause a form of delayed, progressive hearing loss.

The proteins are essentially transducers: They form channels that convert mechanical sound waves entering the inner ear into electrical signals that talk to the brain. Corresponding channels for each of the other senses were identified years ago, but the sensory transduction channel for both hearing and the sense of balance had been unknown.

The channels are the product of two related genes known as TMC1 and TMC2. TMC1 mutations were first reported in people with a prominent form of hereditary deafness back in 2002 by Andrew Griffith, MD, PhD, of the National Institute on Deafness and Other Communication Disorders (NIDCD) and collaborators. Children with recessive mutations in TMC1 are completely deaf at birth.

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Parvalbumin neurons—new insight into the workings of a superhero brain cell

Superhero Cell 6-Parizad BilimoriaSay you’re a scientist in a movie, and you want to find out what gives a superhero his powers. You’d investigate any special suits he wears, whether he drinks any potions and what they are, right? Real-life scientists are following the same strategy to understand a powerful group of specialized brain cells.

Parvalbumin cells (PV-cells) are a population of inhibitory neurons found throughout the cerebral cortex. While small in number and size, they have the impressive capability to synchronize the electrical activities of other brain cells and orchestrate the timing of critical periods, interludes when the brain is more “plastic” and amenable to rewiring. Abnormalities in these pivotal cells are believed to make plasticity go awry, playing an important role in autism, schizophrenia and other neurodevelopmental disorders.

“The PV-cell is vulnerable in many mental illnesses,” says Takao K. Hensch, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s Hospital and professor of molecular and cellular biology and neurology at Harvard University. “So if we can find a way to maintain its health and well-being, then we might have a way to treat neurodevelopmental disorders, even later in life.”

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