Neury Thursday: Mitochondria, neuron health, and sufficient sleep

This paper came out in the Journal of Neuroscience while I was at the Gordon Conference a few months ago. This week, a group did a summary of it in a unique section of the journal called journal club. Basically, it offers a different perspective/interpretation of the data without a loss of content.
In this study, the authors were interested in a structure of the brain stem that regulates sleep-wakefulness: the locus coreleus (LC). Neurons of the LC are considered wake-promoting. To see what happens to the health of these neurons with extended wakefulness, mice were woken up three hours on one day (acute) or eight hours earlier for three days (chronic); mice have a robust and predictable activity period around the lights-on/lights-off transition. Typically, sleep deprivation is done at the end of the night (lights-off/lights-on) so this approach is unique in itself.

With this experimental approach, the biomarker of neuron health that the researchers were concerned about was reactive oxygen species (ROS). Increases in ROS are indicative of harmful physiological stress and likelihood of neurodegeneration. As expected, a gradient of extended wakefulness increased ROS and a near 30% loss of neurons.

Obviously, we can include that sufficient sleep is important for neuron health. But what’s the mechanism? In follow-up experiments, the researchers were concerned with Sirt3–a biological factor of mitochondria–that shuttles byproducts of cellular respiration, namely NAD+. Mice lacking sirt3 had a neuron phenotype similar to mice deprived of sleep; increased ROS and 30% loss of LC neurons.

To conclude, this study adds to the body of evidence showing the neurobiological pathologies and mechanisms related to restricted sleep.

Fifel, K. (2014). Sirtuin 3: A Molecular Pathway Linking Sleep Deprivation to Neurological Diseases Journal of Neuroscience, 34 (28), 9179-9181 DOI: 10.1523/JNEUROSCI.1848-14.2014

The Refs are Biased, Neurologically.

I wrote this blog post during the last World Cup. As the semifinals near, I decided that it would be a perfect time to re-share.

Many of you may remember this lousy foul from the US vs Slovenia match.

Though I initially “jumped to conclusions” and assumed that it resulted from a hefty Slovenian bribe, a recent article in PLOS suggests the call may have resulted from a subconscious bias in reaction time and faulty conclusions of left and right directional movements.

UPenn researchers recruited soccer-knowledgeable fans to view still-frame replays from the English Priemership League (think David Beckham). This league was chosen because aside from David Beckham, ResearchBlogging.orgmany Americans are unfamiliar with the players and teams of this league in addition to limited television viewing within the US. This would reduce the chances of the participants recalling the final outcome of such a play and increase the chances of “unbiasing” directional bias. Kudos to these researchers for taking on the arduous task of blurring out players names and numbers on their jersey’s with Photoshop to eradicate further recall  (many of you are aware of my precipitous hatred for this program!).

Overall, these researchers found that Americans (i.e. individuals who read left to right) react quicker to events that unfold towards the right vs the left. Paradoxically, due to a slower reaction time to left-oriented POVs, participants were more likely to call (or catch) a foul.

I do find it interesting that despite having a slower reaction time to left directional play, fouls are more easily recognized and/or called on the left vs right side. Perhaps this ~100 ms reaction time delay to a left vs right directional play that is unfolding creates a “negativity bias” in that we assume the worst since we aren’t there to witness it….er react quickly enough  (just like we assume that the Slovenian government paid the referees because we weren’t personally there to see if money was slipped from one hand to another….humans love gossip!!!!!!)? Or perhaps the awkwardness of looking right to left causes us to fixate on the left-moving player longer, which leads us to more likely see suspicious activity? This is in contrast to the comfortability of looking left to right, much like reading which involves little fixation on the right-most word and a subsequent rapid transition to the next line. Do we view right directional plays similarly?

Regardless, it would be interesting if this study was replicated to compare cross-cultural differences in directional bias, particularly with societies that read right to left like Hebrew, Arabic, Chinese, and Japanese. Then perhaps this information can be adopted by FIFA to balance cultural -specific POV and ensure a fairer game.

Kranjec A, Lehet M, Bromberger B, Chatterjee A (2010). A Sinister Bias for Calling Fouls in Soccer PLoS One, 5 (7) : 10.1371/journal.pone.0011667

For Jimmie

Two years ago, my cousin was in a life-changing accident. The throttle of his crotch rocket allegedly jammed hurling his passenger and him from his bike. No one knows if he would have been OK with or without a helmet, but he wasn’t wearing one and his brain suffered. Bikers, wear your helmets! Even if you are going to be late, it’s worth it.

Jimmie was a vivacious human being. There was never dull moment in his presence, even more so when my brother was around.
Stars of the Macedonian Convention

The two of them are the protagonists of many stories in Youngstown where we grew up and abroad. That being said, I half expect Jimmie’s calling hours to be sold out!

We love you Jimmie! We know you will keep Grandpa and Grandma entertained in heaven. Grandma may tie your arms around your back a few times but it will be OK.

SRBR 2014: Big Sky, Montana

Conference season continued this month with a week-long trip to the West Coast for the biennial Society for Research on Biological Rhythms meeting which was held in a new location: Big Sky, Montana. Words and pictures cannot describe the serenity and natural beauty of this place. During the many hikes that we took throughout the week, I was constantly reminded of how powerless humans are relative to environmental forces.

Glass lab hike to Oeuka Falls

If I would have taken one step further towards the roaring waterfall pictured below, I would not be writing this at the moment.

Chillin at the falls

The science of the meeting was absolutely wonderful. For me, the conference began with organizing and managing trainee day. This year the keynote speaker was Mich Hastings–former President of SRBR–who is well regarded as a scientist and educator. I really enjoyed Dr. Hastings journey to rhythms work which began on an unexpected, unchartered path of studying invertebrates at a marine biology research station. The most important take-home message of Dr. Hastings’ keynote was to remember that research comes before teaching, all the time. This is not to say that one should neglect their teaching responsibilities, but that at the end of the week, more time should be spent focusing and thinking about research questions over exam questions.

Crossfitting at high altitude

On Sunday, the regular scientific program of the conference began. While most of the talks were not as eloquent and well organized as those of the Gordon conference, there was a wide variety of fascinating work at the basic and translational levels. Somehow people are managing to keep funding rhythms research despite the fact that funding is at an ultimate low. The big focus of this meeting was SCN coupling–understanding how regions of the central circadian clock communicate with each other through the re-investigation of previous work and introducing new neural networks–as well as metabolomics: a buzzword for sure.

For me, my first oral presentation at an SRBR meeting went very well. I was extremely nervous because of speaking to an audience of experts, but the talk really captured interest in my research pursuits of understanding the mechanisms through which the muscle and the brain communicate to influence sleep. My datablitz was also a hit, poking fun of hashtags and Instagram selfies. Needless to say, my brain was overwhelmed by Tuesday evening. The highlight of the meeting was certainly the closing banquet where once again, the Glass lab made a statement. Just check out these pictures below. They may or may not be the most important mode of career development for someone on the job market.

The RABs of the meeting, holding it down

10s for sure

SLEEP 2014: Minneapolis

Nearly every May and June, it is “conference season” for me. A majority of our professional society meetings fall towards the end of the school year. This year is no different. Last week, I was in Minneapolis for the annual sleep meeting which brings together clinical and basic sleep researchers. Next week, I will be in Big Sky, Montana–a first–to attend the Society for Research on Biological Rhythms meeting.

The sleep meeting was a bigger surprise this year because the basic research community finally got paid attention to by the program committee. In years past, the program has been disproportionately focused on clinical research which is important, but it doesn’t represent the sleep community as a whole. Last year, many of us boycotted the annual sleep meeting (myself included) so perhaps it was noticed?

At any rate, Minneapolis is a great place to have a conference because there really isn’t much to do but go to the conference. Sure there are some unique pubs and bars here and there, but the site seeing is a little lacking. Although, I did manage to run along the Mississippi River one day.


Overall, the basic research overlapped with what was presented with Gordon. There were updates in the stories. Once again, I was blown away by the work and presentation of Dr. Mark Blumberg from the University of Iowa. His laboratory studies the functional significances of twitches during sleep, particularly REM sleep. As he has shown, it is near impossible to study how the brain encodes twitches during wake because of all the white noise. During sleep though, it is apparent that the twitches are picked up by areas of the thalamus. Following Dr. Blumberg’s talk, Dr. Markus Schmidt gave a monologue (of sorts) on his interpretation of why sleep is necessary and important. At one point in his life, Dr. Schmidt was an evolutionary biologist and so his energy allocation theory fits with this. In years past, sleep has been thought to exist for the preservation of energy. This is true to some extent. But think about all the processes that require attention paid to while asleep like tissue repair. This is an active, metabolic process, isn’t it?

The meeting would not have been complete without a visit to Chef Gordon Ramsey’s Hell’s Kitchen. One night I had kangaroo there. Apparently kangaroo meat is very high in protein and considered a humane meat source by Aussie ecologists. The second day I had a Juicy Lucifer which is a Minneapolis staple of hamburger meat rolled in cheese.

Learning to Breathe Fire: The History and Science of Crossfit

As a Regionals and Games competitor since the time that Crossfit started to earn the respect of a worldwide athletic company (Reebok) and television network (ESPN), it was enjoyable to re-live the experience through a talented journalist, JC Herz. I will admit that I am not an avid reader of history albeit political, social, or sports-related. I prefer to read popular science as a form of relaxation from my day job as a neuroscientist which is filled with reading highly technical scholarly works saturated with jargon that is rarely found in the OED. That being said, JC Herz has made me re-consider my selections of non-fiction. The level of detail coupled with the writing style of choice made me feel as if I was a spectator or even a fellow athlete during the early years of the Crossfit Games. JC Herz’s literary journey of the 2011 Crossfit Games accurately matched my first-hand experiences of seeing Iceland Annie and “The Champ” (Rich Froning) win their first titles.
JC Herz also did an excellent job combining the history of the sport of fitness with the physiology that underlies elite fitness. It is often a challenge as a scientist or non-scientist to accurately capture the complex physiology and anatomy that underlies athletic performance. JC Herz succeeded beautifully. As a final point, I really appreciated JC Herz’s focus on the heroes of the sport versus its champions. Some of my most emotional moments competing in Regionals and the Crossfit Games are from cheering on those individuals who are obviously struggling get those last few reps. This is the beauty of our sport and the reason why it is so attractive to military and first-responders: no man (or woman) is left behind. The active role that Crossfit plays in the military is another focus of the book and one that may make you shed a tear or two. To conclude, whether you are interested in the history, science, or ethos of Crossfit, “Learning to Breathe Fire” is a must-read for every Crossfitter and fitness enthusiast, beginner or elite.

On sale now!

In Response to the Erin Simmons Dilemma: How to Effectively Defend an Argument

For the crossfitters of the social media world, our FB, Instagram, and Twitter feeds have been littered with a few unique buzzwords the past few days. Of course, this is all in response to Erin Simmons who got her 15 minutes of fame warning society about the dangers of Crossfit. This post is not about defending Crossfit because I do Crossfit, I don’t train others in Crossfit. I’m a student not an educator. However, as a science educator, Erin Simmons’ post is absolutely mortifying for reasons that have nothing to do with Crossfit: Erin Simmons is an esteeming science scholar/educator. I say esteeming because she could easily get a better, tenured-track position at a top-tier university more so than me. This chick was a finalist for a Rhodes scholarship. Rhodes scholarships are (on most occasions) reserved for the brightest minds of the world. Bill Clinton is one of many great minds who received this honor. So, as a Rhodes scholar finalist, a holder of a Master’s degree, and a PhD candidate in the hard sciences at a widely respected research intensive university, one would think that Ms. Simmons would know how to defend a position that is saturated with empirical (versus anecdotal) evidence and is removed of logical fallacies. I became interested in the types of logical fallacies that humans can’t help to make while defending a position from listening to one of the greatest podcasts created for science buffs, geeks, and nerds: The Skeptics’ Guide to the Universe. Seriously, it is awesome. They often have a segment called “Name that Logical Fallacy” on the show. Here is an extremely detailed list with examples of the types of logical fallacies from the SGU website. As an educator, I feel compelled to give my readers a homework assignment tonight and to find as many logical fallacies as [you] can with Erin Simmons’ manifesto. The “Argument from Authority” is just the beginning. Oh, and it doesn’t hurt to watch this Youtube clip of Ms. Simmons executing movements common to a Crossfit regimen with mediocre form in a Crossfit gym. Aside from this, I really hope this chick’s dissertation committee members read her article. There may be some “eeek-ing.” But she is a trainee, and I really do hope that as a trainee who will one day hold a professional, problem solving degree, Ms. Simmons can overcome her hiccups with logical fallacies.

Finally, as Allie Bourdon–a three-time Crossfit Games competitor who has been on the Games podium with her team– beautifully said on Facebook today, it is disrespectful for Ms. Simmons to mention that her friends think that she could be on ESPN doing Crossfit. I don’t doubt that Ms. Simmons could. But immediately? Likely not. Becoming an elite Crossfitter is a process and a commitment, mentally and physically. This video accurately captures the process. Allie and I have both been a part of the process and that is why we have both competed at the Crossfit Games.

Reflection on Crossfit Regionals in Jacksonville (with a lil’ science)

I apologize for the three week hiatus. I’ve been busy preparing for the Reebok Crossfit Regionals and then getting data and experiments ready for a month of conferences (and grant writing) starting next Saturday. This year, I made the commitment to compete as an individual over team. While I find team competition to be more mentally challenging, from the pressure of not being the “weakest link” to communicating with others and not “zoning” out when you are at peak exhaustion, training to compete as an individual is significantly more physically demanding. You are almost doing as much work as one person and at a heavier weight as an entire team of six. I was looking forward to the “gymnasty” events of this Regionals until some really painful rotator cuff impingement set in. Fortunately, my shoulder and pectoral muscles made it through the weekend, and I learned about an amazing, safe, and drug-free supplement in the process; lu rong derived from the middle layer of the deer antler. It stimulates the release of growth hormone via estradiol thereby accelerating joint and tissue repair.

The three-day competition began with a hang (above the knee) squat snatch immediately followed by a handstand walk for distance. I was very pleased about hang squat snatching as much as full snatching and making it across the entire stadium floor for the handstand walk.

Handstand walk for distance

The afternoon workout on Friday was a heavier and more technically challenging version of Nasty Girls which is one of the first workouts created by Crossfit founder Greg Glassman almost ten years ago. It was fun as much as it was painful.

Muscle-ups during Nasty Girls


The second day was the most exciting day of competition. I moved up from the slowest heat to the second fastest heat on day one, and spent the entire second day of competition neck-and-neck with my teammate and long time training partner, Sonya Mac and SAV training partner, Krista Owens. Crossfit Terminus, our gym, was definitely the talk of the day.

Absolutely love this pic!

Many strict handstand push-ups (@56:52 in video #1) and legless rope climbs later (@7:32:06 in video #2), the Crossfit Terminus and Squat Mafia ladies were all sitting in the top 20 with teammate Emily Bridgers leading the region. She dominated every workout, totally sweeping the competition.

The last day began with a grueling, long workout totaling 450 reps. We did a mini-version of it prior to competition and I crawled off the rower. While no woman in our region or the world would go on to finish it, I paced it nicely and finished top three in my heat (@5:53:00 in video #3). With one workout remaining that would go less than an hour later though, my central nervous system decided that it needed some rest.

Muscular fatigue is easier to overcome than neurological fatigue. Usually, the liver and pancreas coupled with protein- and carb-based supplements can replenish sugar, fat, and creatine stores to muscle tissue within a short period of time. With neurological fatigue, however, the recovery can sometimes take days. Obviously, motor neurons must work in order for muscles to contract, extend, and move quickly and your Golgi tendon organs that help stabilize limbs in space and time must be on point as well. Well, my CNS decided that it had enough by the time that I went to pick up a bar that weighted almost as much as me and thrust it over my head to do eight overhead squats after 60+ pull-ups.

around the time my motor neurons and golgi tendon organs wanted a break

I left the competition floor with immediate disappointment and frustration, but about twenty minutes after I threw my weight belt against the wall and kicked an imaginary object, I watched my teammate Emily Bridgers accomplish something she had been hungry and yet patient for across four years: winning the Southeast Regionals and qualifying for the Crossfit Games! It was such an emotional moment for all of us at the gym–teammates, coaches, and gym members–as much as it was for her. Until the Games which will be broadcasted on ESPN in July, the Terminus crew looks forward to pushing Em any way we can to get that podium spot. She’s a fierce one, watch out!

Panda Nation with the Champ


Characterizing Sleep-Wake States in a Cat

For those of you not schooled in the history of sleep, the use of a cat as an animal model of sleep may seem novel. However, the cat was used as an animal model of sleep decades before rats, mice, hamsters, monkeys, and other non-human mammals. In fact, one of the first studies to identify sleep- versus wake-promoting centers in the brain was done in cats by Frechman, Michael Jouvet.

ResearchBlogging.orgIn 2012, the electrophysiological techniques available to better characterize sleep and wake states in the brain are certainly much more advanced than the tools available in the early 1900s. The researchers of this study used a single electrode to record from a distinctive cell population in the thalamus. The general idea was to see how the electrical firing of the neurons would change across different stages of sleep (NREM and REM) and wake and to see how transitions into specific sleep states impacted activation of the somatosensory cortex. In brief, this is a model of memory consolidation and to determine if a particular stage of sleep regulates such memory consolidation.

In order to record in the cats, the cats were trained to be restrained. I’m not sure how this was undertaken and how the cats would voluntarily become comfortable with such restraint let alone being prodded with electrodes. I envision the training being similar to that in one of the classic South Park episodes when the boys learn that cat urine can make them wicked high by restraining a cat and making it watch another video of aggressive cats: an activity known as “cheesing.”

Here is a snapshot of the data. Looks beautiful, doesn’t it. The main finding was that there was a temporal relationship between transitions into NREM sleep and the evoking of the somatasensory cortex. These experiments were also investigated in the slice and was one of the first instances of documenting sleep in the dish.

LFP recordings of sleep and wake


In conclusion, I was pleased to see that with all the technology that we have available today in basic biomedical research, researches still see value in historical model organisms and approaches. Both are equally as valuable for uncovering mechanism as any new technology.

Chauvette, S., Seigneur, J., & Timofeev, I. (2012). Sleep Oscillations in the Thalamocortical System Induce Long-Term Neuronal Plasticity Neuron, 75 (6), 1105-1113 DOI: 10.1016/j.neuron.2012.08.034

Daylight Savings is a Public Health Concern. Who is responsible? The circadian system or sleep homeostat?

This isn’t new news. For years, public health officials have forewarned us about the increased risks for car accidents, workplace accidents, and immediate declines in cardiovascular and neurological health following the springing forward. Nearly all of these studies attribute the connection between DST and changes in health risks to an hour of sleep loss because an opposite trend emerges when we fall back; there’s a decrease in these phenomena. This week, I decided to take advantage of ResearchBlogging.orgthe neuroscience institute’s experts in sleep and circadian rhythms and members of the cardiovascular institute in the same room for our quarterly journal club, and present a paper relevant to DST and changes in the incidence of myocardial infarctions. The findings of this paper published in 2013 are not novel but relevant. The study was a retrospective examination of hospital records from nearby hospitals in Michigan across six years (2006-2012). What is relevant about this study is that the landmark studies were from a Swedish database, making it difficult to extrapolate to US lifestyle because the Swedes are the healthiest industrialized nation in the world, while we are among the unhealthiest. The Swedes have a diet rich in antioxidants and anti-inflammatory factors and are much more active than their American counterparts who crave and live off of processed foods. That being said, isn’t the Swedish study a more convincing case for DST being a public health concern since their general population is already at a reduced risk compared to us? Yes, I believe so. But still, it is important to have a direct assessment of US health.

Here is a snapshot of the demographics of this study which included about 1,000 people. Most were in their early 70s. Nearly 50% had some cardiovascular event (major or minor) in the past, had been taking statins to control high blood pressure and cholesterol, and even other meds like aspirin. Surprisingly, very few had been diagnosed, about 3%, with sleep apnea or some type of sleep disorder.

Study demographics

When it came to looking at the incidence of heart attacks from falling back versus springing forward, the same trends as those in the Swedish study appeared. There was a reduction in risk on the Sunday of falling back and an increase in risk a few days after springing forward. Great. What the researchers failed to mention or statistically compare or to graph in an interpretative manner is that there is a higher incidence of heart attack at the start at the work week (Monday) in all cases;  in the groups of people going in for heart attacks around DST and even for the control groups who had a heart attack two weeks before or after DST. What is this about?

comparison of US vs Swedish study

There were other seasonal affects as well such that springing ahead caused an increase in non-segmented heart attacks which result in partial damage to the cardiac muscle unlike segmented (full-blown) heart attacks. But the biggest issue here is that there is little mention of circadian contributions to these results. Yes, sleep is important, but an hour sleep gained or lost no matter how big the sleep debt is prior is trivial compared with the constant changes in social and environmental factors on a weekly basis. We are constantly flip-flopping back and forth from weekday to weekend schedules which result in different rise times, bed times, meal times, play times, etc that can wreak long-term havoc on physiological and behavioral systems since there is a constant need for re-entrainment. To me, social jet lag, less so environmental jet lag is the culprit in this study and the preceding landmark study, but this term along with any mention of “circadian” are omitted from both the introduction and discussion sections. It looks like physicians need some schooling on chronobiology….

Jiddou MR, Pica M, Boura J, Qu L, & Franklin BA (2013). Incidence of myocardial infarction with shifts to and from daylight savings time. The American journal of cardiology, 111 (5), 631-5 PMID: 23228926

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