Genomics plus human intelligence

The power of gene sequencing to solve puzzles when combined with human Read more

'Master key' microRNA has links to both ASD and schizophrenia

Recent studies of complex brain disorders such as schizophrenia and autism spectrum disorder (ASD) have identified a few "master keys," risk genes that sit at the center of a network of genes important for brain function. Researchers at Emory and the Chinese Academy of Sciences have created mice partially lacking one of those master keys, called MIR-137, and have used them to identify an angle on potential treatments for ASD. The results were published this Read more

Shape-shifting RNA regulates viral sensor

OAS senses double-stranded RNA: the form that viral genetic material often takes. Its regulator is also Read more

cerebellum

Cells in “little brain” have distinctive metabolic needs

Cells’ metabolic needs are not uniform across the brain, researchers have learned. “Knocking out” an enzyme that regulates mitochondria, cells’ miniature power plants, specifically blocks the development of the mouse cerebellum more than the rest of the brain.

The results were published in Science Advances.

“This finding will be tremendously helpful in understanding the molecular mechanisms underlying developmental disorders, degenerative diseases, and even cancer in the cerebellum,” says lead author Cheng-Kui Qu, MD, PhD, professor of pediatrics at Emory University School of Medicine, Winship Cancer Institute and Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta.

The cerebellum or “little brain” was long thought to be involved mainly in balance and complex motor functions. More recent research suggests it is important for decision making and emotions. In humans, the cerebellum grows more than the rest of the brain in the first year of life and its development is not complete until around 8 years of age. The most common malignant brain tumor in children, medulloblastoma, arises in the cerebellum.

Qu and his colleagues have been studying an enzyme, PTPMT1, which controls the influx of pyruvate – a source of energy derived from carbohydrates – into mitochondria. They describe pyruvate as “the master fuel” for postnatal cerebellar development.

Cells can get energy by breaking down sugar efficiently, through mitochondria, or more wastefully in a process called glycolysis. Deleting PTPMT1 provides insight into which cells are more sensitive to problems with mitochondrial metabolism. A variety of mitochondrial diseases affect different parts of the body, but the brain is especially greedy for sugar; it never really shuts off metabolically. When someone is at rest, the brain uses a quarter of the body’s blood sugar, despite taking up just 2 percent of body weight in an adult. More here.

Also, see this 2017 item from Stanford on the cerebellum (Nature paper).

Posted on by Quinn Eastman in Neuro Leave a comment

New molecular target in dystonia

Emory researchers led by pharmacologist Ellen Hess have identified a new molecular target in dystonia. Their findings, recently published in the Journal of Pharmacology and Experimental Therapeutics, could help doctors find drugs for treating the movement disorder.

Ellen Hess, PhD

Dystonia gives sufferers involuntary muscle contractions that cause rigid, twisting movements and abnormal postures. It is the third most common movement disorder, after tremor and Parkinson’s disease. Neurologists can sometimes use drugs to address the symptoms of dystonia but there is no cure.

A 2008 review by Hess (PDF) concludes that compared with other neurological disorders, “our understanding of the biology and potential treatments for dystonia is in its infancy.” Still, scientists have known for a while that the cerebellum, a region of the brain that regulates movement, is involved.

“We focused on the cerebellum because studies in patients with dystonia often show that this part of the brain is more active, when examined by MRI,” Hess says. “The abnormal overactivity of the cerebellum is seen in patients with all different types of dystonia, so it seems to be a common hotspot. Our goal was to understand what might be causing the overactivity in mice because if we can stop the overactivity, we might be able to stop the dystonia.”

Hess and her colleagues discovered that drugs that stimulate AMPA receptors induce dystonia when introduced into the mouse cerebellum. Their results suggest that drugs that act in reverse, blocking AMPA receptors, could be used to treat dystonia.

Postdoctoral fellow Xueliang Fan is the first author of the paper. Emory neurologist H.A. Jinnah, director of a NIH-supported network of clinical research sites focusing on dystonia, is a co-author.

AMPA receptors are a subset of glutamate receptors, a large group of “receiver dishes” for excitatory signals in the brain. Fan performed a variety of experiments to show that AMPA receptor activity plays a specific role in generating dystonia. For example, drugs that affect other types of glutamate receptors did not induce dystonia. AMPA receptor blockers can also reduce dystonia in a genetic model, the “tottering” mouse.

Although pharmaceutical companies have already been testing AMPA receptor blockers as potential antiseizure drugs, caution is in order. AMPA receptor stimulators/ enhancers (or “ampakines”) have been identified as potential enhancers of learning and memory, so AMPA receptor blockers may interfere with those processes.

“Our results suggest that reducing AMPA receptor activity could help alleviate dystonia but we still have a lot of work to do before we know whether blocking AMPA receptor activity in patients will really help,” Hess says. “Since there aren’t many drugs that act at AMPA receptors, one of our goals is to identify drugs that change the ‘downstream’ effects of AMPA receptor activation. For example, we may be able to find other drug classes that change neuronal activity in the same way that AMPA receptor blockade changes activity.”

Posted on by Quinn Eastman in Neuro Leave a comment