Saturday, December 24, 2011
Thursday, December 22, 2011
Attention college students. Which of the following scenarios sounds familiar to you?
1) You have just pulled 3 all-nighters and did terribly on your exam because you could not stay awake.
2) You have just pulled 3 all-nighters, you made the mistake of taking a “nap”…and now all you can do for the next few days is sleep. So yeah, you got that extension on the paper, but are still unable to turn it in on time.
Yep, we’ve all been there. But rejoice, we finally have an alibi. It’s really not us—it’s our immune systems! …Or is it? Faraut, et al., in this paper, have hown a link between sleep deprivation and our immune system. Essentially, they have confirmed that when we are sleep deprived, certain aspects of our immune systems flare up. That flaring up can only diminished with napping or with an extended period of “recovery sleep”. In fact, the authors show that napping is even more effective at regulating immune responses than extended sleep.
For this study, Faraut, et al. plucked out 40 young, healthy men and subjected them to a series of screening tests (after paying them, of course). First, all 40 participants had to fulfil the following criteria:
They had to be:
2) Not regular nappers (but slept regular nights for 7-9 h)
3) Between 19-25 in their BMI
4) 18-27 years old
5) Free of diseases and sleep-complaints
They were also put through various tests: psychiatric, as well as medical, screenings, sleep questionnaires, polysomnography to monitor their sleep patterns, and CRP and leukocyte concentrations to determine each individual’s healthy, non-inflammatory levels. The actual experiment itself was carried out as follows (Fig. 1):
[ Fig. 1 ]
After the third “Recovery” day, Faraut, et al. looked at 4 things: the peripheral blood leukocyte count, the level of peripheral blood inflammatory and athergenesis biomarkers, the individual sleepiness of the participants and their cortisol levels. The authors saw that in all experimental groups, the leukocyte (white blood cell) and neutrophil (inflammatory white blood cells) levels increased significantly after the “restricted” night in which they had only 2 hours of sleep. However, the group that had a half-hour nap along with their recovery sleep (Group 2) and the group that had extended sleep (Group 3) were able to decrease this spike in leukocyte/neutrophil expression. This downregulation of leukocyte levels was not evident in the group that had the recovery sleep alone (Group 1).
The researchers performed a sleepiness assessment test based on the Stanford Sleepiness Score, and the Maintenance of Wakefulness Test. The results of this test mirrored the leukocyte/neutrophil results. They saw that across all three groups, there was a uniform increase in sleepiness at 1:30 pm after sleep restriction. In looking at each recovery group, they noted that Group 1 was a lot sleepier at 3 om than Groups 2 and 3. However, Group 3, which had the extended sleep period, was sleepier compared to the nap-takers (Group 2). They also saw that after restriction, the nap-takers had fewer onsets of sleep (none), whereas extended sleepers and normal sleepers (Group 1) had 1 and 2 onsets of sleep, respectively. This indicates that napping is more condusice to restoring alertness after a period of sleep deprivation, which is consistent with other studies that have been done on napping (1).
The authors also monitored what they call the subject’s “sleep architecture”, which is the kind of sleep an individual experiences. There are basically two kinds of sleep: slow-wave sleep (SWS) and Rapid-Eye Movement (REM). SWS represents a period of deep, restful sleep, whereas REM indicates a lighter sleep experience (dreams, which are often rare during deep sleep, occur during REM). Since results indicate that napping seems to provide a better path to recovery than just 8-hours of recovery sleep, or even an extended, 10-hour recovery sleep, Faraut, et al. determined that simple a half-hour of deep, SWS sleep can drastically reduce the homeostatic pressures of sleep. Therefore, deeper sleep, especially in short bouts, prevents our immune system from going into overdrive and our bodies from trying to regulate that abrupt change.
So how does our immune system play into all of this? Well, sleep deprivation triggers various inflammatory responses from our immune system. Studies have shown that pro-inflammatory cytokines such as IL-8, IL-6, and TNF-a are secreted following chronic partial or total sleep deprivation (2, 3). Additionally, these inflammatory responses can bring about cardiovascular disease (2, 4). Faraut, et al. were not able to see significant increases in IL-8, CRP, or fibrinogen as they had expected. They did manage to see, on the other hand, increases in MPO (myeloperoxidase) levels immediately after sleep deprivation. This is significant because MPO is an peroxidase enzyme that defines the granulocyte function of neutrophils (ie., neutrophils release it to chew things up). MPO also catalyzes the formation of oxidizing agents that eventually bring about atheromatous plaque.
Sleep deprivation and the subsequent increase in peripheral blood leukocytes, therefore, has implications in causing cardiovascular mortality. This is consistent with studies that have shown that there is a higher risk of cardiovascular diseases in shift workers (5). Conversely, midday napping has also been shown to be inversely associated with coronary mortality (6).
Interestingly enough, a study by van Mark, et al. (7) speculates that chrinic sleep dept (almost like insomnia) is common in shift workers, possibly as a protection mechanism against an overstimulation of pro-inflammatory immune mechanisms. This makes sense because we are able to 3 to 4 consecutive all-nighters, and feel relatively fine while doing so. This is due to the suppression of the homeostatic actions of our bodies. However, as soon as we go to sleep, we seen to never be able to wake up. This is likely due to the fact that our immune responses are finally kicking in, and our bodies are naturally trying to make up for the cytotoxic damage caused by the inflammatory responses.
How does all this information help us college students then? It doesn’t, really. This post merely serves as a warning that if we willingly pull all-nighters, we are setting ourselves up for a domino effect of immune responses and the homeostatic pressures exerted by our bodies in response. That, and cardiovascular disease. So, yes, technically, it really isn’t our fault that we’re not able to “heal” enough and in time to hand in our overdue assignments in time for their extended deadlines. But at the end of the day, who told us to pull an all-nighter (let alone 3) to begin with?
Faraut, B., et al. (2011). Benefits of napping and an extended duration of recovery sleep on alertness and immune cells after acute sleep restriction. Brain. Behavior, and Immunity. 25:16-24.
1) Takahasi, M., Arito, H. (2000) Maintenance of alertness and performance by a brief nap after lunch under prior sleep deficit. Sleep. 23:813-819.
2) Meier-Ewert, et al. (2004) Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J. Am. Coll. Cardiol. 43:678-683.
3) Redwine, L., et al (2010) Effects of Sleep and Sleep Deprivation on Interleukin-6, Growth Hormone, Cortisol, and Melatonin Levels in Humans. J Clin Endocrinol Metab. 85:3597–3603.
4) Irwin M.R., et al. (2010) Sleep loss activates cellular markers of inflammation. Arch. Intern. Med. 166;1756-1762.
5) Puttonen, S., et al. (2010) Shift work and cardiovascular disease—pathways from circadian stress to mortality. Scand. J. Work Environ. Health. 36:96-108.
6) Naska, A., et al. (2007) Siesta in healthy adults and coronary mortality in the general population. Arch. Intern. Med. 167:296-301.
7) van Mark, A., et al. (2010) The impact of shift work induced chronic circadian disruption on IL-6 and TNF-a immune responses. J. Occu. Med. And Toxicology. 5:18-22.
Monday, December 19, 2011
Not Exactly Rocket Science
Sunday, December 18, 2011
Saturday, December 17, 2011
There are a number of diseases spread in this manner, termed transmissible spongiform encephalopathies (TSE). All TSE's, which include the well-known mad cow disease (Creutzfeldt-Jakob disease), are inevitably fatal and lead to neurodegeneration, often mediated through pathologic neuroinflammation. The inflammation seems to be primarily due to the robust activation of microglial cells (Yang et al., 2008). Microglial cells are akin to the brain’s garbage trucks, constantly collecting cellular debris from the extracellular environment. This behavior coincidentally makes them especially fit for detecting the presence of extracellular pathogens as well.
Before a cure can be developed, researchers must first uncover the cellular mechanisms underlying the microglial-medated pathologic neuroinflammation observed in the victims of TSE. PrP106-126 is the region of the PrP protein that has been shown to mediate inflammatory and pathologic signaling following structural alteration. A recent study was able to use this peptide to identify many of the proteins and signaling molecules, thus potentially uncovering future targets for pharmaceutical therapies.
Pictorial representation of RA (http://www.rumatory-arthritis.com/)
Rheumatoid arthritis (RA) is a debilitating chronic autoimmune disorder that leads to the synovial inflammation of joints and surrounding tissues. The clinical prognosis is the irreparable destruction of cartilage, tendon, and bone in affected joints and the disease can progress aggressively, especially without proper treatment.
Friday, December 16, 2011
In order to study MS, researchers often employ the use of animal models. Specifically, Experimental Autoimmune Encephalomyelitis (EAE) is a well recognized mice model that mimics the progression of MS. EAE is considered a Th1 focused disease with T cells secreting primarily IFNϒ. T cells are immune cells in the body that participate in cell-mediated killing of foreign pathogens (1). In MS, they recognize our myelin as a foreign substance and proceed to destroy it. One way they do this is by secreting cytotoxic cytokines, such as the aforementioned IFNϒ. When inducing EAE in mice, this Th1 response is ensured by injecting a myelin peptide(to mount an immune response against) along with complete Freunds adjuvant (CFA), which contains a bacterium called M. Tuberculosis (CFA).
Aside from IFNϒ, IL-23 has emerged as a notable cytokine because mice deficient for it remained protected against EAE pathology. Furthermore, IL-23 promotes the differentiation of inflammatory Th17 cells (2). Numerous EAE models currently exist; some more representative of MS in certain clinical regards (e.g., onset, clinical progression, and remission). Therefore, it’s vital to always explore new EAE models in an effort to find one that best represents human MS. In a recent study by Smith et al. 2011, researchers replaced M. tuberculosis with C. rodentium (CRA)in the injected adjuvant. CRA is a bacteria known to induce an IL-23 dependent Th17 response (as opposed to the aforementioned M.tuberculosis-mediated Th1 response) to find out whether different EAE phenotypes would emerge.