Research Briefs

NICHD: EARLY STAGES IN MUSCLE FORMATION AND REGENERATION DISCOVERED

NICHD scientists have identified proteins that allow muscle cells in mice to form from the fusion of the early-stage cells that give rise to the muscle cells. The findings have implications for understanding how to repair and rehabilitate muscle tissue and for understanding other processes involving cell fusion, such as when a sperm fertilizes an egg, when viruses infect cells, or when specialized cells called osteoclasts dissolve and assimilate bone tissue in order to repair and maintain bones.

Muscle cells originate from precursor cells known as myoblasts, which fuse to form a single long, tubular cell called a myocyte (a muscle fiber). Muscle tissue is composed of large collections of these fibers. The fusion of myoblasts into muscle fibers takes place early in fetal development. With exercise and throughout a person’s life, the process is repeated to form new muscle mass and repair old or damaged muscle.

To study myoblast fusion, the researchers first blocked the start of the fusion process with a chemical. Ordinarily, the mouse myoblasts fuse at varied intervals. By blocking fusion and then lifting the block, the researchers were able to synchronize fusion in a large number of cells, making the process easier to study.
The researchers identified the two distinct stages of cell fusion and the essential proteins that facilitate these stages. In the first stage, two myoblasts meet, and proteins on cell-surface membranes cause the membranes to meld. In the second stage, a pore opens between the cells and their contents merge. This second step is guided by proteins inside the cells.

The work identifies two cell-surface proteins that act at the start of myoblast fusion. These proteins belong to a large family of proteins called annexins, which are known to play a role in membrane repair and in inflammation. The researchers also identified the protein dynamin, found inside the cell, as essential to the second stage of the cell-fusion process. Dynamin also has an unexplained link to certain rare and poorly understood myopathies—disorders characterized by underdeveloped muscles. The researchers hope that further examination of the role of dynamin in cell fusion will lead to a greater understanding of these conditions. (NICHD authors: E. Leikina, K. Melikov, S. Sanyal, S.K. Verma, B. Eun, C. Gebert, K. Pfeifer, V.A. Lizunov, and L. V. Chernomordik; J Cell Biol 200:109–123, 2013)


NIAAA: ADVANCING THE UNDERSTANDING OF MOVEMENT CONTROL

Voluntary movements involve the coordinated activation of two brain pathways that connect parts of deep-brain structures called the basal ganglia, according to a study in mice by NIAAA researchers. The findings challenge the classical view of basal ganglia function that proposes that direct and indirect pathways originating in a brain region called the striatum have opposing effects on movement. Neuron activity in the direct pathway is thought to promote movement, while activity in the indirect pathway is thought to inhibit movement. Newer models suggest that co-activation of these pathways is necessary to synchronize basal ganglia circuits during movement, but until now it’s been difficult to test them.

The NIAAA researchers, however, devised a new approach that uses fiber-optic probes implanted in the mouse brain striatum to measure light emissions from neurons engineered to glow when activated. Using probes, the researchers detected neural activity in both the direct and indirect pathways when mice performed a bar-pressing task. No such activity was detected when the mice were inactive.

The scientists hope that a better understanding of how the basal ganglia control movements will lead to treatments for disorders in which these circuits are disrupted such as Parkinson disease, Huntington disease, and addiction. In addition, the new technique will be useful for studying a variety of neuron types in other brain regions. (NIAAA authors: G. Cui, X. Jin, M.D. Pham, S.S. Vogel, D.M. Lovinger, R.M. Costa; Nature 494:238–242, 2013)


NIEHS: H1N1 FLU SHOTS ARE SAFE FOR PREGNANT WOMEN

Norwegian pregnant women who received a vaccine against the 2009 H1N1 influenza virus showed no increased risk of pregnancy loss, whereas pregnant women who experienced influenza during pregnancy had two-fold risk of miscarriages and stillbirths, according to a study by NIEHS researchers in collaboration with scientists in Norway. (NIEHS authors: S. Haberg and A. Wilcox; N Engl J Med 368:333–340, 2013)


NCI: INCREASES IN RISK OF CERTAIN LEUKEMIAS RELATED TO TREATMENT

A new NCI study describes the pattern of risk for one form of cancer, acute myeloid leukemia (AML), that has risen over the past three decades for adults who have previously been treated with chemotherapy for other forms of cancer, notably non-Hodgkin lymphoma (NHL). The increased risk among NHL survivors could be due to prolonged survival in recent years for some lymphoma subtypes that are associated with multiple courses of chemotherapy. The findings are based on data from NCI’s Surveillance Epidemiology and End Results cancer registries to evaluate the risk of leukemia in more than 426,000 adults who had been diagnosed with cancer between 1975 and 2008 and who had received chemotherapy as part of their initial cancer treatment. Among these patients, the authors identified 801 people who subsequently developed AML.

Over the study time period, the researchers observed declining risk among patients treated for ovarian cancer, myeloma, and possibly lung cancer. The decreased risk among patients with ovarian cancer is consistent with a shift from use of a certain alkylating agent—associated with the risk of developing leukemia—to platinum-based chemotherapy in the early 1980s. The authors also found evidence that the risk of treatment-related AML has increased since 2000 among patients treated for esophageal, prostate, and cervical cancer and since the 1990s among patients treated for cancers of the bones and joints and of the endometrium.

Future studies are needed to gather information on the risks associated with specific chemotherapy agents, which could not be obtained from this study. (NCI authors: L.M. Morton, G.M. Dores, M.A. Tucker, C.J. Kim, E.S. Gilbert, J.F. Fraumeni, Jr., and R.E. Curtis; Blood DOI:10.1182/blood-2012-08-448068)