Fly through a mouse brain!

What do you do when you want to see what is inside a mouse's head?

In the past, you had to:
1. Find a mouse.
2. Kill said mouse.
3. Remove brain (the mouse's, not your own).
4. Fix brain (even if it wasn't broken to begin with) in formaldehyde or some other chemical.
5. Embed brain in wax.
6. Cut brain into teeny tiny slices.
7. Try to get one of those slices to sit flat on a slide.
8. Stain the brain slice.
9. Look at it under an expensive microscope.
10. Try to figure out what you are looking at.

Now, through the wonders of modern Interwebology, you need not go through the toil and trouble and smell. Now we have The Mouse Brain Library. For the librarians among my loyal readership, this is not the kind of library where you walk through the stacks until you find a brain on the shelves that might look interesting, then check it out with your library card.

No, indeed. This is the kind of library that lets you look inside a mouse's brain without leaving the comfort of your favorite coffee shop. You can even watch movies.

Here's my favorite. It's a trip through a mouse head, starting at the top and going down. This one shows structure of the surrounding head, as well as the brain. The nose is to the right and the back of the head is to the left. You can see the eyes, white circles at the top and bottom of the image. Between them lie the olfactory bulbs, responsible for smell. (The sense of smell that is. The smelliness comes from the other end of the mouse.) You can also see the spiraling chambers of the nasal cavities.

And that ends our tour through a mouse's head. I hope you enjoyed it. Watch your step as you leave the tour bus.

Yeah, but what happens if you smoke it?

A compound in oregano and basil has been shown to have antiinflammatory effects in mice. The compound, called (E)-beta-caryophyllene or(E)-BCP, is also found in large amounts in rosemary, cinnamon, and black pepper. And Cannabis sativa, a.k.a. marijuana.

The most well-studied components of marijuana, cannabinol and tetrahydrocannabinol (THC), exert their effects by binding to two receptors, CB1 and CB2. CB1 is expressed in the brain and other tissues and is responsible for the ...elevating...effects of Cannabis sativa. CB2, on the other hand is primarily found in tissues outside the brain. Activation of CB2 has been shown to inhibit inflammation.

This paper describes some experiments showing that (E)-BCP binds to CB2, but not CB1. They did all the stuff you are supposed to do in the lab to demonstrate its binding qualities, then they tested the compound in mice.

They dissolved (E)-BCP in (appropriately) olive oil and fed it to mice. Then they injected the footpads of the mice with carrageenan, which makes the footpads swell. The feet of the mice that had been fed (E)-BCP had much less swelling than the mice that had been fed olive oil alone. This antiinflammatory effect was not found when they used mice in which the CB2 receptor had been knocked out, demonstrating that it was the CB2 receptor activation that was responsible for the beneficial effect.

I knew pesto pizza had to be good for you.

Did they make it to the top?

Here's a story in the Philadelphia Inquirer about the murine Everest ascent.
Here's a blog about it.
Here's some video.

The answer: almost.
The real answer awaits the arrival of the mouse blood from Nepal...and some lab work. Not as glamorous as mountain climbing, I know, but that's science for you.

Don't believe everything you read

Sara Latta brought this photo to my attention. I'm not going to reproduce it here. It's a prime example of what happens when people place their own agendas ahead of scientific accuracy.

On October 11, 1999, a nude mouse appeared in a full-page ad in The New York Times, sporting what appeared to be a human ear growing out of its back. The caption described it as “an actual photo of a genetically engineered mouse.” A group protesting unregulated genetic research had placed the inflammatory ad, but it was not exactly accurate. The mouse was not genetically engineered at all. It was a normal nude mouse. Nor was the ear human. It was a product of the laboratory of Charles Vacanti.

Vacanti wanted to improve replacement options for patients who have lost an outer ear (or other cartilage-based structure) due to injury, burns, or birth defects. Plastic implanted under the skin can become infected and is not very durable. An ear sculpted from the patient’s cartilage may not be shaped satisfactorily. Vacanti used a synthetic polymer, similar to that used in dissolvable sutures, to sculpt an outer ear. He then implanted it under the skin of a nude mouse, along with cartilage cells from the legs of calves. Because nude mice do not reject tissue from other animals, the calf cartilage cells could survive and grow in the nude mouse.

The mouse's body provided the necessary environment for the cartilage cells to attach to the polymer scaffold, eventually replacing the scaffold, which dissolved away. The result was cartilage in the perfect shape of a human ear.

Although the result was bizarre-looking, especially in the already bizarre-looking hairless mouse, it was very effective. The technique has since been used successfully in humans, producing replacement cartilage structures from human cartilage cells on polymer scaffolds implanted into the patient’s body.

The mouse was later to be called the Vacanti Mouse or the "earmouse." Unfortunately, its bizarre appearance was used to promote the anti-science agenda of the group that ran the ad. Take a photo out of context, add some half-truths and outright lies, and you can convince the public of almost anything.

That is why we need to promote scientific literacy.

Distant relatives?

In response to a comment from Moonrat, I have done a bit of genealogical research, hoping to discover some long lost rodent relative. I was skeptical because Moonrat's appearance seemed to me to be more possum-like than rat-like. Quite reminiscent, in fact, of the opossum that sometimes engages in moonlight raids of my compost bin.

Alas, Moonrat is but a distant mouse relation. Native to the Malay Peninsula, Sumatra, and Borneo, the moonrat (Echinosorex gymnura), also called Raffles's gymnure, is an insectivore, more closely related to the hedgehog than the mouse.

Sorry there's no relation, Moonrat. Give my regards to your Aunt Tiggy-Winkle.

Where no mouse has gone before

Yes, mice are climbing Mount Everest as I post. They look so cute in their little parkas, and you should see the tiny little crampons they are wearing on their feet!

OK, I made up the part about the parkas and crampons, but the rest is true.

Scientists from the University of Pennsylvania, led by Tejvir Khurana, are carrying lab mice to the top of the world. This article, from New Scientist, describes how the mountain-climbing scientists will be testing the mice for changes associated with extreme altitude. The ultimate purpose of the study is to find a way to detect athletic doping.

As I discussed in a previous post, athletes often train at high altitudes so that their bodies make more red blood cells, improving their performance. The hormone responsible for the increase in red blood cells is erythropoeitin, or EPO. In the past, doping athletes used synthetic EPO to boost their blood cells, but there is now a test that can distinguish synthetic from naturally-produced EPO. Dopers could potentially get past that hurdle by using other substances (like mustard oil?), or even genetic manipulation, to stimulate the natural processes that induce EPO.

The researchers hope to stay one step ahead of the dopers by identifying markers in the tissues of blood of mice at high altitude. These markers could then be used in an anti-doping test to identify natural EPO produced by unnatural means as opposed to natural EPO produced in response to the perfectly legal practice of training at high altitude.

Now that's a claim to fame I can live without: first scientist to bleed a mouse at the summit of Mount Everest.

I think I'll have a cup of hot chocolate, now.

A Twist of Lyme

My dear husband, Smintheus, came home earlier this week looking less than his usual robust self. He soon spiked a fever. Since he had been camping and morel hunting in a Lyme endemic area the two previous weekends, I took him to the clinic for some doxycyline. Although he didn't have a documented tick bite, several in his party did, and the ticks are so small at that stage, they would be easily missed. The doctor agreed that it would be prudent to treat the disease as Lyme, since the blood test is often inconclusive and early treatment can prevent serious long-term consequences.

"Here she goes again," you say. "Another off-topic post."

Stay with me.

Lyme (not Lyme's) disease was named for the town in Connecticut where it was first identified. It is caused by the bacterium Borrelia burgdorferi, transmitted to humans by the black-legged tick, also known as the deer tick. This tick (Ixodes scapularis) has a complex two year life cycle. From the common name of the tick, you would expect to find them associated with deer, and they are.

But they also feed on mice, and it is the mice that are the source of the infection.

The ticks only take a blood meal two or three times in their lives. The first, which is usually from a mouse, allows it to mature from a larva to a nymph. It is the nymphal stage that is most likely to bite humans, especially in the late spring and summer. The second blood meal (which can be from a variety of animals, including humans) allows the nymph to mature into an adult tick. The female takes a third blood meal from a deer so that she can lay eggs.

Deer are important for the life cycle of the ticks and for carrying them around and spreading them through the environment, but they aren't infected by the Lyme bacterium.

It's our friend the mouse, specifically the white footed deer mouse (Peromyscus leucopus), that is the major reservoir. Up to 90% of mice in some areas are infected with the Lyme bacterium.

Here is a fascinating discussion of the ecology of Lyme disease and how the prevalence and transmission are affected by deer, mice, weather, acorns, and human behavior. Here is a paper (and a more user-friendly press release) about mouse vaccination as a way to interfere with the transmission of Lyme disease.