Sunday, October 25, 2009

A new kind of mind control

Remember subliminal messages? Those images supposedly flashing too quick for your mind to register, but still managing to convince you to drink more soft drinks, eat more fries, buy a luxury car? While those days may not be over yet, new forms of mind control (albeit more biological than psychological) are emerging thanks to the tiniest of creatures, the bacteria.

A friend of mine, Cal, recently alerted me to an interesting article about optogenetics. If you’re not familiar with the word, that’s because it’s very new, and it essentially means playing with light and genetics at the same time. It’s all the rage in neuroscience right now and articles such as the one I’ll be describing in this post are popping up every week.

It all starts with a tiny little pump called halorhodopsin found in bacteria. This pump sits at the surface of cells and pumps chloride ions from outside the cell to the inside (table salt is sodium chloride - same chloride). Cells use chloride for different reasons, but this pump can be especially relevant for brain cells (called neurons). Neurons pass information to one another through electric currents. And it just so happens that chloride ions are charged negatively. That means that if many chloride ions accumulate inside a neuron, the cell becomes increasingly charged negatively, making it harder to reach the positive threshold it needs to pass currents to other neurons.

Other types of chloride pumps already exist in your brain cells, but almost nobody makes a fuss about those. So how is halorhodopsin different? This is where the “opto” from “optogenetics” comes in. This particular pump is activated by light. This means that if neurons have this special pump, you can control whether they are active or not just by flashing a light onto them.

In a recent paper published in PNAS, the researchers genetically engineered zebrafish so that their brain cells expressed the special light-activated chloride pump. The researchers then recorded the electrical signals generated by the brain cells (they look like spikes, much like what you would see on an EEG). I don’t know if you can imagine what kind of feat that represents, but I’d like to make a motion to modernize the saying “like finding a needle in a haystack” to “like poking an electrode into a brain cell of a live fish”. Once they knew what the signals looked like in normal conditions, they shone the light on the fish*, and amazingly, all the brain cells went quiet. It worked! The light activated the pump, negatively charged chloride ions accumulated in the cells and made it too difficult to reach the spiking threshold.

The black lines are the current spikes that normally occur when brain cells transmit information. The yellow section is when the researchers shone the light: no more spikes.

Now a fish doesn’t have that many brain cells to start with, and since it spends most of its life moving it’s pretty safe to assume that a large portion of the fish’s brainpower is devoted to swimming. The researchers thought they had a pretty cool tool to test this, and so they did. They put a bunch of genetically-engineered zebrafish in a dish, watched them swim around for a bit, and then shone a light on them*. Sure enough, the fish stopped moving and lost coordination. I realize we’re talking about lousy, bottom-of-the-food-chain fish here, but think about it: *that’s* mind control.

The article continues to great lengths, going into details about what specific part of the brain controls the swimming behavior and describing control experiments that confirm that this isn’t a fluke (i.e. the fish aren’t just spooked by the light). All things considered, it’s a very elegant example of how to use optogenetics to better understand the brain. And the relevance of these advances lies in the increased understanding of not only the brain but also diseases of the brain. Recently, these new techniques used in animal research gave us important insights into Parkinson’s disease.

What about using these tools as ways not only to understand disease, but also to treat them? What if we made our own brain cells express this special pump so we could use light to activate or inhibit different areas of our brains? While this may seem like science fiction right now, don’t be so sure. I attended a talk on optogenetics recently, and the researcher firmly believed that this emerging field of neuroscience would eventually cure blindness. In the meantime, let’s see if you can think of all the ethical questions this would raise…

* For these experiments, the researchers used fish in the larvae stage. The skin of the fish at that point is transparent, and this allows the light to reach the brain cells.

This little zebrafish is doing his best to contribute to science.

Reference: Optical control of zebrafish behavior with halorhodopsin. (2009) Arrenberg, A.B., Del Bene, F., Baier, H. Proc Natl Acad Sci USA, 106(42):17968-73.

Monday, October 12, 2009

Yet another reason for a good night's sleep

How much do you sleep at night?

If you’re like most of the people I know, the answer is “not enough”. There’s a reason Starbucks coffee shops are popping up literally meters away from one another. Everybody has a reason to be sleep-deprived: new kid, big job, World of Warcraft, etc. So what if we’re cutting the night short a few hours? Other than the need for an overpriced coffee (or two, or three), it should be just fine, right?

Maybe not, if you believe the latest research on sleep and Alzheimer’s disease.

Alzheimer’s disease, a debilitating form of memory loss and cognitive decline, is the most common form of dementia. It is thought to be caused at least in part by amyloid beta (A-beta), a peptide (short protein). Your brain cells (neurons) normally make some A-beta. The problem that arises with Alzheimer’s disease is that neurons make too much A-beta, and these molecules aggregate together in chunks. It’s those A-beta chunks that are toxic, and their formation is concentration-dependent, which means the more A-beta you have floating around, the higher the probability of toxic chunks forming.

The recent article published in the journal Science looks at levels of A-beta in the brains of normal mice and in the brains of a mouse model of Alzheimer’s disease. The researchers studied the mice when they were 3 months of age, so well before big deposits and chunks of A-beta start occurring.

The interesting finding of this study is that the levels of A-beta in the brains of both types of mice were significantly correlated with the amount of time they spent awake. More time spent awake lead to more A-beta. Because the control, normal mice also exhibited this relationship, it means that it is not linked to the disease. It’s just a normal fluctuation of A-beta levels linked to the sleep-wake cycle. To be certain this link was relevant for human physiology, they also tested this in healthy humans and, sure enough, they observed the same correlation.

Not surprisingly, when the researchers proceeded to sleep-deprive the mice, they showed an even larger increase in A-beta levels. This increase was also observed when the mice were given a drug that promotes wakefulness (don’t extrapolate this to coffee just yet… But maybe keep it in mind…). The study also points out that the Alzheimer mice who are sleep-deprived showed much greater numbers of A-beta chunks (the toxic stuff) compared with non sleep-deprived mice.

If you come to Scientific Chick for relevant findings, this one is for you. The study essentially implies that optimizing sleep time could potentially inhibit the formation of chunks of toxic A-beta and slow the progression of Alzheimer’s disease.

We all know that Alzheimer’s disease is terrible, and that sleeping in is glorious. Let’s just put two and two together, shall we? Easier said than done, I know…

Mr. Minou gave up on caloric restriction but approves of this new approach to ward off age-related diseases.

Reference : Amyloid-{beta} dynamics are regulated by orexin and the sleep-wake cycle. (2009) Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, Fujiki N, Nishino S, Holtzman DM. Science Sep 24. [Epub ahead of print]

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