How a Heart Fails

July 10, 2015

By Medical Discovery News

A heart

What exactly causes a heart to fail? It may come down to a simple protein, which scientists recently identified as having an important role in how a heart goes from weakening to failing.

Your heart is a strong, muscular pump slightly larger than your fist that pushes blood through your body. Blood delivers the necessary oxygen and nutrients to all cells in all the organs. Every minute, your heart pumps five quarts of blood. Human hearts have four chambers: two atria on top and two ventricles on bottom. Oxygenated blood leaves the lungs, enters the left atrium, moves to the left ventricle, and is then pumped out of the heart to the rest of the body. After it circulates, blood returns to the heart, enters the right atrium, moves to the right ventricle, and is then sent back to the lungs for a fresh dose of oxygen. Although your heart beats 100,000 times each day, the four chambers must go through a series of highly organized contractions to accomplish this.

Any disruption of this process can have serious consequences such as heart failure, which is clinically defined as a chronic, progressive weakening of the heart’s ability to circulate enough blood to meet the body’s demands. To compensate, the heart enlarges, which increases contractions and the volume of blood pumped. Blood vessels elsewhere in the body narrow to keep blood pressure normal. Blood can even be diverted from less important organs, ensuring more vital organs like the brain and heart are satisfied. However, such responses mask the underlying problem: the weakening heart, which continues to worsen. Ultimately, the body can no longer compensate for the heart, which is when it will start to fail.

Scientists at the University of California, San Diego School of Medicine studied the cellular changes in weakened hearts to better understand the transition from the compensatory stage, when it works harder to pump blood, to the decompensation, when it fails to pump blood sufficiently. They were especially interested in a RNA-processing protein called RBFox2 because it is involved in the heart’s early development and its continuing functions. When genes are expressed, DNA is transcribed into RNA, which is then processed and eventually used to make proteins such as RBFox2.

Sure enough, levels of RBFox2 were dramatically reduced in the hearts of mice with a condition similar to heart failure. Then they genetically engineered mice without RBFox2, which developed symptoms of heart failure. Not only are low levels of this protein connected to weakened heart muscle, without enough of it, the body cannot compensate and the heart declines more quickly. However, we still don’t know why levels of RBFox2 decline during the transition to the decompensatory phase of heart failure.

In the future, this research might be used to develop treatments that reverse the decline of RBFox2 and effectively slow or prevent heart failure.

For a link to this story, click here.

Why Don’t We Bite Our Tongues?

Dec. 26, 2014

By Medical Discovery News

Why We Don't Bite Our Tongues

Why don’t we normally bite our tongues when we eat? A recent study found that two types of cells in brain, the premotor neurons and motoneurons, work together to coordinate the movements of the jaw and tongue, so that you do not usually bite your own tongue.

We can control chewing consciously, but otherwise it works automatically. Coordination of jaw and tongue muscles during eating is one of the most intricate mechanisms of the motor system in animals and humans. The coordination concerns both the timing and the sequence of muscle activation, in order to achieve the smooth and effective motions required when eating.

Three basic systems must be coordinated when eating. First, activity of the left and right jaw muscles must be symmetrical. Second, the tongue must be coordinated to position food between the teeth while the jaw moves the teeth to break down the food during chewing. Finally, jaw opening and tongue protrusion must be coordinated with jaw closing and tongue retraction to prevent the tongue from getting in between rows of sharp teeth.

Muscles in the jaw and tongue are controlled by brain cells called motoneurons, and those are then controlled by premotor neurons. The previously unsolved mystery was exactly which premotor neurons connect to which motoneurons, which then control muscles. To find the answer, scientists engineered a rabies virus to map the signals that control chewing. The bullet-shaped rabies virus was useful for this study because it infects muscle cells and peripheral neurons and moves rapidly up the nerves to the central nervous system, where it replicates in the brain.

Scientists at Duke University in North Carolina took advantage of the rabies virus’s ability to migrate up peripheral neurons toward the central nervous system, so they could map the circuitry that controls chewing. The disabled rabies virus migrated from muscles to motoneurons and then to premotor neurons. They also added a fluorescent green or red tag to the virus so scientists could track the virus on its journey.

Scientists injected this virus into two muscles: the genioglossus muscle that controls tongue protrusion and the masseter muscle that is involved in jaw closing. They discovered that one group of premotor neurons connect to both these muscles. A separate group of premotor neurons regulates tongue retraction and jaw opening. Sharing premotor neurons to control multiple muscles is an elegantly simple system to coordinate the movements of the tongue and the jaw to protect the tongue from a painful bite. The body cannot close the jaw automatically without also retracting the tongue.

This study was conducted using only mice, and it is only the beginning of understanding how chewing is controlled. At least 10 other muscles are active while chewing, drinking, and speaking. Additional studies will be needed to map all the motoneurons and premotor neurons involved in the complex, orchestrated movements that accomplish what are seemingly simple and routine tasks.

For a link to this story, click here.

Motivate Me

By Medical Discovery News

Oct. 27, 2012

The real challenge for all of us is to get to the gym

Anyone with a TV has seen them – the skinny, smiling men and women who claim to have lost weight without breaking a sweat thanks to diet pills. But most diet pills carry health risks like increased blood pressure and heart rate, insomnia, and stomach cramps. Some carry more risks than others, such as Orlistat, which was taken off the market after people developed liver failure.

Yet even that didn’t dash the hopes of dieters searching for a magic pill, which could be pinned on a completely new approach – a hormone that boosts a person’s desire to exercise. Swiss scientists found that when a hormone called erythropoietin (EPO) was elevated in the brains of mice, they were more active.

EPO is the same performance-enhancing hormone banned by various sporting events and leagues including the Olympics and the Tour de France. During the 1998 Tour race, personnel from several teams were caught red-handed with thousands of doses of EPO and other banned substances.

Athletes are tempted to use EPO because it has the ability to increase red blood cells in the bloodstream, which translates to more oxygen circulating throughout the body and consequently better physical performance. The hormone exists naturally, produced by cells in the kidney that can sense when oxygen levels start to dip.

EPO travels in the bloodstream and into bone marrow where it binds with receptors to stimulate red blood cell (erythrocyte) production. Medically, EPO is used to treat certain forms of anemia. Since EPO accelerates erythrocyte production, it increases the blood’s capacity for carrying oxygen.

Even though the body makes EPO, using more of it comes with risks. In the past 15 years, about 18 cyclists have died suddenly in their sleep from using EPO. When injected repeatedly in small doses, EPO stimulates the release of more red blood cells. In some cases, too many red blood cells are produced, which can thicken the blood, clog capillaries, and lead to a stroke or heart attack. Athletes face a greater risk since they tend to become dehydrated, further thickening the blood.

However, researchers at the University of Zurich found that when given in acute high doses (500 – 2,000 times more than what athletes use), EPO crossed the blood-brain barrier and helped mice run better. The mice had not produced more red blood cells nor increased their cardiovascular capacity. So EPO acted as a brain hormone that motivated the mice to exercise more, without changing their physiology.

Beyond helping many Americans who are obese, EPO may quicken recovery for people who have been bedridden and need to rebuild muscle mass. This treatment approach has not yet been tried on humans, so it will take time for researchers to determine its effects and efficacy.

For a link to this story, click here.