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]

Dating advice courtesy of your friendly neighborhood monkey

Dating advice websites abound with many different kinds of advice: good advice (don’t pick your nose), strange advice (date according to your blood type), not so good advice (Leos dating Leos need to hire domestic helpers). One suggestion that seems to pop up quite frequently is to mimic the body language of your date. He picks up his drink for a sip, you pick up yours. He strokes his hair, you stroke yours. He picks his nose, you pick your nose. You get the idea. As it turns out, in a social interaction context, we humans tend to unintentionally imitate what others are doing. Think of this as a team-building exercise: it’s a behavior that helps establish rapport, empathy and other fuzzy feelings toward each other.

A recent publication in the journal Science shows that behavior matching leading to increased rapport is not exclusive to humans, and it can also occur between different species.

The study looks at capuchin monkeys, a very social primate species. During the experiments, the monkey is given a ball to play with. On either side of the monkey’s cage stands an experimenter. One experimenter is mimicking what the monkey is doing with the ball (poking it, pounding it against the wall, trying to eat it… Mmmmm…), while the other experimenter is also playing with the ball, but not mimicking the monkey. The researchers show that not only do the monkeys look at the imitators more, they also spend more time hanging out close to the imitators and prefer to interact with the imitators in a food exchange game. The authors also did an important series of control experiments to show that these effects were not due to the monkeys perceiving more attention from the imitators.

So why are we subconsciously hard-wired to constantly be playing Simon Says? It is thought that the positive feelings resulting from behavior matching played an important role in human evolution by leading to higher levels of tolerance and by preventing aggressive behavior (to put it simply, by preventing us from beating each other up). The same principle probably applies to primates, and the empathic connection that results from imitation may explain the altruistic tendencies observed in the behavior of capuchin monkeys.

Next time you catch yourself winking back at someone who winked at you, or laughing at a joke you didn’t get because everyone else is laughing, keep in mind it’s for the greater good. After all, even monkeys know that imitation is the sincerest form of flattery.

Scientific Chick readers applying their new found knowledge
(Image from Loldogs)

Reference: Capuchin monkeys display affiliation toward humans who imitate them. (2009) Paukner, A., Suomi, S.J., Visalberghi, E., Ferrari, P.F. Science 325:880-882.

The fountain of youth revisited

Not too long ago, I wrote about my love of brownies and an article on caloric restriction. I wasn’t really planning on bringing up this topic again so soon but a recent Science paper on caloric restriction in monkeys is getting so much media attention that I just had to throw in my two cents.

In the article, a group of American researchers study control and calorie-restricted (30%) monkeys over 20 years. What they show is that the calorie-restricted monkeys have a reduced incidence of age-associated death, diabetes, cancer, cardiovascular disease and brain atrophy compared to the control monkeys. From the sounds of it, we can stop looking for the fountain of youth (it’s in Florida, by the way). The media absolutely loves this story, and news reports and videos are quick to claim that caloric restriction increases longevity in our closest cousins, and it must be good for us as well.

First, a disclaimer from the friendly folks at ScientificChick.com: In the recent years, solid, convincing and well-controlled studies have shown some benefits of caloric restriction in various types of experimental subjects ranging from yeasts to humans. I won’t go back into the pros and cons of caloric restriction in this post. There is good evidence out there that it can be beneficial in some instances, and also good evidence that it’s not for everyone.That being said, I believe there are many problems with this particular Science paper on caloric restriction.

In my opinion, a major issue with the findings is that the control monkeys (the ones not on caloric restriction) are fed ad libitum (meaning they can eat as much as they want). You might be able to guess the problem already, but let me give you an example just in case: I have a cat, and if I were to offer him a constant supply of what seems to me like gross, bland cat food, he would keep eating it until he would slip in a food coma. I think this goes for most species, including us (ever heard of the candy jar experiment?). Therefore, it’s very hard to judge if monkeys who eat as much as they want are eating the amount of food they should naturally be eating. Chances are they are eating more (breakfast, lunch and dinner are not served at regular hours in the wild). And this is particularly relevant because eating too much (or obesity) happens to be an important risk factor for all the diseases the study looks at (diabetes, cardiovascular problems, cancer, etc.).

Another issue with the article is that few of the findings show a statistically significant difference between the control and the calorie restricted groups, even though the researchers are studying a reasonably large number of monkeys. When your results are statistically significant, it means that what you are observing is unlikely to have occurred by chance. This concept is a hallmark of solid and convincing science findings and the media should be very careful not to hype findings that aren’t statistically significant. In addition, almost every single news article on this publication claimed that caloric restriction had an effect on longevity. While the study looks at age-associated diseases, the longevity (or life expectancy) parameter is not assessed at all (though the researchers do mention they plan on assessing this in the future).

Lastly, and perhaps most disturbing from my scientist point of view, the lead researcher in this study happens to be co-founder and member of the board of LifeGen Technologies, a company focusing on the impact of dietary interventions on the aging process. A little research on this company made it very clear to me that the more people buy this whole caloric restriction business, the more money the company makes. If that’s not a conflict of interest, I don’t know what is.

Now if you’ll excuse me, a new cupcake store just opened across from my building, and I must significantly increase the quality of my life by going over and eating a cupcake.

My cat, Mr Minou, is not a fan of caloric restriction.

Reference: Caloric restriction delays disease onset and mortality in rhesus monkeys. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R. Science. 2009 Jul 10;325(5937):201-4.

Your brain's reset key is Zzzz

As a teenager, like many of you I’m sure, I neglected sleep. It seemed that partying all night and then working hard at school all day was the obvious solution to an overbooked schedule. I was rudely awakened a few years later when a good night’s sleep became necessary to merely function the next day (also when I realized what it really meant to have an overbooked schedule). While we know that sleep is essential for survival (at some point, coffee just doesn’t cut it), we know very little about why sleep is so important, and what happens to our brain while we sleep. In a recent issue of Science, a team of researchers made a contribution to this field using sleep-deprived fruit flies.

In the study, researchers looked at synapses, the junctions between brain cells (called neurons). Synapses are important because they relay information from one neuron to the next. Through synaptic connections, neurons form networks, and these networks underlie many complex brain functions like perception and thought.

The researchers cleverly engineered fruit flies to make their synaptic connections fluorescent (for those of you who read my first post, this is an excellent use of GFP). Subsequently, the researchers took images of the flies’ brains, and were able to count the brightly fluorescent synapses. The study first established that flies that hang out with other flies (this is called social enrichment) have more synapses than lonely flies. While this finding is interesting on its own, the researchers didn’t stop there. They took the socially enriched flies and divided them in two groups. The first group of flies was allowed to sleep as much as they wanted for 48 hours while the second group of flies was sleep deprived for 48 hours. Which group of flies do you think had more synapses after the experiment?

Well, the study shows that flies that slept had much fewer synapses than the sleep-deprived ones. Does it surprise you?

Initially, I thought this was a little counter-intuitive. With all this talk about sleep being important for performance and memory, I would have thought that the flies that slept would have had more connections between brain cells. This study suggests exactly the opposite, and shows that sleep acts to downscale the synapses that are created while the flies are awake and experiencing new things. When you think about it, this finding makes sense. If there was no way to “reset” those synapses, we can hypothesize that every time you learn or experience something new, you would get more and more connections between your brain cells. Eventually, we can imagine it would be a complete mess up there, and connections might saturate, leaving no room for anything new. Downscaling your synapses at night while you sleep also helps eliminate the unimportant connections, thereby making the stronger synapses stand out.

So what’s the take-home message? Enough procrastinating on the internet, go to bed!

Reference: Use-dependent plasticity in clock neurons regulates sleep need in Drosophila. Donlea JM, Ramanan N, Shaw PJ. Science. 2009 Apr 3;324(5923):105-8.

Emotional forecasting: The weather man is your friend!

Some of you may recall my earlier success at understanding article titles in the journal Science. Well, I did it again! I score another 100% with a fascinating study published this week titled “The surprising power of neighborly advice”.

The researchers begin their article by insulting us, suggesting that we are terrible at guessing how we’re going to feel about future events. I personally disagree, I’m pretty sure I know just how good it’s going to feel to one day finish my PhD! I’m going to be ecstatic! I’m going to be elated! I’m going to cry with joy! You get my point. Anyway, the researchers suggest otherwise, saying we often overestimate how happy we’d be to say, win the lottery (yeah, right!), as well as overestimate how unhappy we’d be to say, not get a promotion. That’s because our strategy to estimate our reaction to future events is to imagine them, but apparently we’re bad at that too (so far, it’s not looking good). So we make mistakes. But there is hope! Their research suggests that we can get a better idea of how we’ll feel during future events, all we need to do is ask a friend.

The study revolved around speed dating (quite a sexy topic when it comes to science!). Women were told they were going on a 5 minute “speed date” with a guy, and they were given one of two types of information about the guy. The first type of information was a document with the guy’s profile: his picture, his background, activities he enjoys doing (long walks on the beach, no doubt), his favorite movie, book, etc. This is called “simulation” information because it made it possible for the woman to imagine what the date would be like. The second type of information was a document with another woman’s appreciation of a speed date with the same guy. This is called “surrogation” information because the woman going into the date can use the woman who already met the guy as a surrogate for herself. Just before meeting the guy, the woman had to tell the researchers how much she thought she’d enjoy the date based on the information she got. After the date, she gave a report of how much she actually did enjoy the date.

The outcome of the study is two-fold. First, the women were way more accurate in their prediction of how much they’d enjoy the date if they used surrogation information (another women’s point of view). Second, opposite to what worked best in reality, most of the women believed that simulation information would allow them to make the most accurate prediction about their date. Even more surprising, over 80% of the women indicated they would chose simulation over surrogation information to make a prediction about a future date with a different guy.

How is this relevant? Well, it tells us that the best way to make a decision that’s right for us is to get advice from others. It also tells us that we tend not to take advantage of this type of information, even though it can be quite useful. A great example of surrogation information is “review” websites such as epinions and dinehere. When going to buy their next electronic gizmo or dine out at a new restaurant, more and more people will check for neighbourly advice online rather than just trusting the ‘specs’ or the menu. There’s nothing like the cover of anonymity to tell the world what you really think of it…

After reading this study it sounded like I needed to double check just how I’ll feel about finishing my PhD with my fellow labmates who’ve been there, and yes it’s confirmed: I’ll be crying with joy. And doing the happy dance.

Cartoon courtesy of Doug at www.savagechickens.com

Had a bad day? Erase your memories!

The reputable scientific journal Science just published an interesting article about memories called “Selective Erasure of a Fear Memory”. I especially like the fact that I understand 100% of the words in the title (unlike another article from the same issue, “Generation of Follicular B Helper T Cells from Foxp3+ T Cells in Gut Peyer's Patches”, where I score a meagre 46%).

How memories are stored in the brain has always been a mystery. It is thought that each memory is stored in the form of a group of brain cells (neurons), but it’s practically impossible to confirm that because those neurons are all over the place. We do know, however, that a brain region called the lateral amygdala (LA) is where fear memories are stored. Say you’re just a kid and your older sibling decides to make you watch Poltergeist (am I the only one who went through this?). During the really scary parts of the movie, your neurons in the LA make a ton of this protein called CREB (yet another acronym, it stands for cyclic adenosine monophosphate response element binding protein). That’s the tell-tale sign the researchers used to try to identify and then destroy the neurons responsible for fear memories.

They used an experiment called fear training (sounds like torture? Just think about all the people who willingly volunteered to be on “Fear Factor”). They put a mouse in a special cage, and then they play a tone. Right after the tone, the mouse gets a little shock on its feet. The mouse eventually catches on, and freezes when the tone is played (freezing behavior is how we know the mouse is scared). The really clever part of this experiment is that the researchers managed to engineer in the mouse a genetic switch that would selectively kill the neurons that made a lot of CREB (the ones presumably responsible for the fear memory). So after training the mouse to be scared of the tone, they flipped the switched on, the CREB-making neurons died, and voilà! The mouse forgot its fear of the tone and no longer freezes.

So, ok, researchers fried part of this mouse’s brain, and the mouse won’t freeze anymore. Sure, but will the mouse do anything anymore? I don’t know about you, but I’m picturing the mouse in a post-lobotomy state, drooling a little, unmotivated to do anything. Apparently not so. The researchers did a bunch of control experiments to show that the mouse could still run through mazes, store new memories, and even re-learn to be afraid of the tone, if properly trained. They also showed that if you just kill a bunch of random LA neurons (instead of just the ones that make lots of CREB), erasing memories doesn’t work.

So is this relevant? Well, it’s a great contribution to our knowledge of how memories are encoded and stored. A lot of people are excited about this because they see a potential therapy for post-traumatic stress disorder, but to be fair, applications in humans are very, very far down the road, regardless of what the movie “Eternal Sunshine of the Spotless Mind” suggests. If you had a choice, would you erase some bad memories of your past? How did those memories shape the person you are today?