EPO

If you are a fan of the Tour de France bicycle race, you know all about EPO, or erythropoietin.

EPO is naturally found in the body and its normal function is to induce the production of red blood cells, or erythrocytes. Since the red blood cells carry oxygen, more red blood cells mean more oxygen available to the muscle, which in turn means improved athletic performance.

As a drug, EPO is used to treat conditions like anemia, but it can also be used (illegally) to boost an athlete’s red blood cell count. The Tour de France is a grueling race, and many are tempted to make it a little easier. If you are caught using EPO, you are kicked out. EPO is part of a long history of doping in the Tour, and cycling in general.

The body can make more EPO naturally, under conditions of low oxygen, or hypoxia. That’s why people living at high altitudes, where there is less oxygen, have more red blood cells. It's also why Tour de France competitors often train at high altitude.

Proteins in the lungs called hypoxia-inducible transcription factors (HIFs) sense the low oxygen and induce the production of more EPO to make more red blood cells. HIFs are also present in the skin of frogs. Since amphibians can breathe through their skin, this makes sense. What is surprising is that these people found HIFs in mouse skin, too.

They wanted to see if skin HIFs had any functional significance in mice, so they rigged up chambers in which they could control the oxygen content of the air the mice breathe independently of the air that contacts their skin. They found that low oxygen levels at the skin increased EPO, but not in mice in which HIF expression in the skin was knocked out. That means that HIFs in the skin are involved in hypoxia-induced EPO production.

Part of the skin’s response to low oxygen includes increased blood flow. When they applied nitroglycerine patches (which increase blood flow) to the skin of mice, EPO levels also increased.

Another substance that increases blood flow in the skin is mustard oil (allyl isothiocyanate). This also increased EPO in mice. The authors note that it is common practice in Pakistan and Nepal to massage the skin of newborns with mustard oil and they speculate that this practice might increase the production of EPO and thus red blood cells in the babies. (Here’s the paper.)

So the next time you smell mustard oil at the Tour de France, you will know why.

Mind control

Yesterday, I wrote about how male mice respond to the smell of the urine of female mice—they sing.

The subject for today is bobcat urine and how an infection can change a mouse’s response to it.

Normally, when a mouse smells a cat (or a fox), it runs away. I mean, it makes sense, given the gustatory preferences of cats. It’s pretty Darwinian, too. Mice that run away when they smell a cat are more likely to survive than mice that hang around.

Toxoplasma gondii is a parasite that can infect mice, cats, and humans. It’s the reason pregnant women are advised not to change their cat’s litter box. Here’s why:

The life cycle of the parasite requires that it spend some time in cats, to undergo the sexual portion of its reproductive cycle. Normally it gets into cats when cats eat an infected mouse.

This paper describes how Toxoplasma gondii makes it more likely that it will complete its life cycle. It controls the minds of mice. The investigators studied both rats and mice infected with Toxoplasma gondii. Control animals spent as little time as possible near bobcat urine or a collar that had been worn by a cat. Infected animals spent more time near the catty items. Not only were they not afraid of cat smells, they were attracted to them.

This wasn’t just a generalized anxiety effect, and it was specific for predator smells. Infection didn’t affect their behavior around rabbit urine or novel foods.

The parasite changes the brains of mice in such a way that the mouse is attracted to the very predator that is required for the parasite to reproduce.

There is even some evidence that Toxoplasma gondii infection affects human behavior, and that it may play a role in schizophrenia.

Yet another reason to stay away from cat poop.

If you're happy and you know it...

Male mice make ultrasonic vocalizations that, when slowed down enough for us to hear, sound like songs. Listen here.

This study looked at what makes them sing. The answer: female mice.

They sing when they smell the urine of female mice, but not rats or humans.

They sing when they can touch female mice, but not if they can only see them.

And they sing when they are...um...interacting with female mice.

But they don't sing as much when certain brain receptors have been knocked out.

Muscarinic receptors (in this case M2 and M5), are necessary for dopamine release. Dopamine is a neurotransmitter that plays a role in motor control, emotion, sexual behavior, and scads of other functions.

If you don't have dopamine, you are not happy.

So mice without M2 and M5 receptors are not happy and they aren't likely to sing. I wonder if they only sing the blues.

Now let's see what drugs can do. (Mice on drugs!) When they give these guys amphetamines, which activate dopamine, they sing more. Except if they have had the M5 receptor knocked out.

The authors propose that ultrasonic vocalizations can be used to measure positive affect in mice.

In other words, you can tell how happy a mouse is by listening to it sing.


Here's the paper.

It's a gas

Meet Joseph Priestley (1733-1804).

He discovered the pencil eraser and carbonated water, essentials for Sudoku and Diet Coke, respectively.

Aside from those critical discoveries, his most important contributions to science had to do with the chemistry of air. He is generally known as the discoverer of oxygen, but it was Priestley who first proposed that air is not a single element (as in air, water, earth, and fire), but was made up of a mixture of gases.

Priestley may have been one of the first scientists to use mice in research. Using a candle, a mouse, and a sprig of mint, he demonstrated that oxygen (as it was later dubbed by Antoine Lavoisier) is needed to keep a candle alight and a mouse alive. He also showed that, although flames and mice use up oxygen, plants produce it. That's photosynthesis.

He discovered a lot of gases. Along with oxygen, there was carbon dioxide, carbon monoxide, ammonia, nitrous oxide (laughing gas), and hydrogen sulfide.

Hydrogen sulfide is the gas that give rotten eggs their rotten smell. High doses are lethal. A recent study has shown that when mice inhale small doses of hydrogen sulfide, their hearts and metabolisms slow down and their bodies use less oxygen. (Here's the paper.) It's like hibernation, but without the cold. Some also call it suspended animation. The effect is completely reversible with no apparent ill effects.

Hydrogen sulfide allows mice to survive in conditions of low oxygen. If it's true (and safe) for humans, too, then it could buy some precious time in the ER.

Back to the eighteenth century. Not only did Priestley demonstrate that oxygen kept mice alive, but more was better. Extra oxygen added to the glass chamber enhanced mouse survival.

"Had it been common air, a full-grown mouse, as this was, would have lived in it about a quarter of an hour. In this air, however, my mouse lived a full hour; and though it was taken out seemingly dead, it appeared to have been only exceedingly chilled; for, upon being held to the fire, it presently revived, and appeared not to have received any harm from the experiment."

He also tried some of this stuff himself and felt "peculiarly light and easy for some time afterwards." A man truly ahead of his time.