Syndicate content

Archive - Jan 8, 2018


Appetite Control Depends on Signaling at Primary Cilia in Brain Neurons, UCSF Mouse Study Shows

University of California-San Francisco (UCSF) researchers have discovered that the brain's ability to regulate body weight depends on a novel form of signaling in the brain's "hunger circuit" via antenna-like structures on neurons called primary cilia. Primary cilia are distinct from motile cilia, the finger-like projections that act as a sort of cellular conveyer belt, with functions such as removing debris from the lungs and windpipe. Immotile primary cilia were once thought to be vestigial, like a cellular appendix, but in the past decade, research at UCSF and elsewhere has revealed that these structures play a key role in many forms of hormonal signaling in the body. Now, the new UCSF study, published online on January 8, 2018 in Nature Genetics, shows that primary cilia also play a crucial role in signaling within the brain. The article is titled “Subcellular Localization of MC4R with ADCY3 at Neuronal Primary Cilia Underlies a Common Pathway for Genetic Predisposition to Obesity.” Neuroscientists are accustomed to thinking of brain signaling in terms of direct chemical or electrical communication among neurons at sites called synapses, but the new findings reveal that chemical signaling at primary cilia may also play an important, and previously overlooked role. In addition, the findings suggest potential new therapeutic approaches to the growing global obesity epidemic, the researchers say. "We're building a unified understanding of the human genetics of obesity," said senior author Christian Vaisse, MD, PhD, a professor in the Diabetes Center at UCSF and a member of the UCSF Institute for Human Genetics.

Study Reveals Reversibility of Friedreich’s Ataxia in Novel Mouse Model

Friedreich’s ataxia is an inherited disease that causes damage to the nervous system and a loss of coordination that typically progresses to muscle weakness. It can begin causing symptoms in childhood or early adulthood and, over time, it can also lead to vision loss and diabetes. Scientists seeking a better understanding of the disease have tried for years to replicate the disease’s symptoms and progression in laboratory mice, but until recently have been largely unsuccessful. Now, a team of UCLA researchers has recreated aspects of Friedreich’s ataxia in mice and shown that many early symptoms of the disease are completely reversible when the genetic defect linked to the ataxia is reversed. The findings were published online on December 19, 2017 in eLife. The open-access article is titled “Inducible and Reversible Phenotypes in a Novel Mouse Model of Friedreich’s Ataxia.” “Remarkably, most of the dysfunction we were seeing in the mice was reversible even after the mice showed substantial neurologic dysfunction,” said Dr. Daniel Geschwind, the Gordon and Virginia MacDonald Distinguished Chair in Human Genetics, a UCLA Professor of Neurology and Psychiatry, and the study’s senior author. “We were very surprised by the extent to which the mice improved.” The results, however, need to be replicated in humans before researchers know whether they can lead to new therapeutics for people with Friedreich’s ataxia. Friedreich’s ataxia is known to be caused by a genetic mutation in a gene called FXN. The mutation leads to reduced levels of frataxin, the protein encoded by FXN. Although doctors can manage some of the symptoms, there are no treatments for the disease.