Winding Up Your Body’s Clock

clock of circadian rhythm

Scheduled physical activity is found to help regulate and amplify the body’s circadian rhythm. This suggests a way for curing defective circadian rhythms and a multitude of diseases that have been linked to malfunctioning circadian rhythms. 

 

Animals, including humans, utilize clocks called circadian rhythms to keep the body aligned with nature’s daily night and day cycle. The circadian rhythm is controlled by the suprachiasmatic nucleus in the brain. The circadian rhythm is a daily cycle of behavioral and physiological functions regulated by fluctuating levels of hormones. Malfunctions in the circadian rhythm often develop in the elderly and a recent study found these malfunctions in the circadian rhythm may be to blame for a myriad of diseases including diabetes, cancer, cardiovascular disease and mood disorders [Arendt J (2010). Occup Med (Lond) 60, 10–20.]. A study published in the December 2012 Journal of Applied Physiology found that scheduled physical activity strengthens and regulates the circadian rhythm (Voluntary scheduled exercise alters diurnal rhythms of behavior, physiology and gene expression in wild-type and vasoactive intestinal peptide-deficient mice, 2012. Analyne M. Schroeder, et al.).

In the study mice were given varying levels of access to a running wheel: no access, free access, late night access and early night access. By measuring ambulatory activity, body temperature, heart rate and circadian rhythm hormones the researchers found that having scheduled access had a strong control over their circadian rhythm. Even free access versus no access had an effect. Mice are naturally active at night. The figure below shows how varying access to running wheels affected their ambulatory activity.

Ambulatory activity in wild-type mice as a function of time of day in response to no, free, early night and late night access to running wheels.

Even more interesting was the effect of the running wheel access variable in vasointestinal polypeptide (VIP) deficient mice. VIP deficiency leads to circadian rhythm loss of function. Late night running wheel access was able to restore many of circadian physiological and behavior cycles to those seen in the wild type (VIP normal) mice. One of the molecular clocks measured was PER2 and Luciferase, the ratio of which corresponds to different points in the circadian rhythm. The figure below compares this molecular clock with wild type mice.

A measurement of PER2::Luc ratios in VIP deficient mice (VIP -/-) as a result of varying access to a running wheel. The dotted lines represent the levels seen in the wild-type mice.

What this study shows is that not only can exercise be important for therapy, but the time that exercise is performed is also important. For people who perform exercise on a daily basis, maintaining a standard workout schedule is beneficial because our bodies are “ready to go”at the workout time each day. Apparently, this readiness does not require our normal circadian rhythm machinery as evident by the VIP deficient mice’s ability to get on a schedule. Further research is needed to show that scheduled physical activity can help elderly patients suffering from a loss of circadian rhythm function.

Concussions in the NFL lead to Depression

football

 

Professional football players who suffer from a concussion are more likely to develop long-term mental health episodes such as depression.

 

The prevalence of concussions in football has significant mental health ramifications. One concussion occurs every 2.44 NFL games. A study published in the American Journal of Sports Medicine looked at correlations between concussion incidences and depression (Nine-Year Risk of Depression Diagnosis Increases With Increasing Self-Reported Concussions in Retired Professional Football Players, 2012. Zachary Y. Kerr, et al.).

The study used a 2001 General Health Survey sent to the 3,729 members of the NFL Retired Players Association. A second General Health Survey was sent nine years later in 2010. The surveys asked questions regarding the respondents physical and mental health as well as the number of concussions suffered during their professional careers. Those exhibiting depression in the first survey were not used in the study.

Of the players who reported never having a concussion, only 3.0% were diagnosed with depression. Of those who reported suffering from 10 or more concussions, 26.8% were found to suffer from depression. The relationship between number of self-reported concussions and likelihood of suffering from depression was a linear relationship. Those who reported suffering from 3 or more concussions were twice as likely to suffer from depression as those reporting 1-2 concussions over their career and three times more likely than retired professional football players who did not suffer any concussions over their professional career.

Work on depression in US soldiers in Iraq has suggested there may be a link between tauopathies, tau protein deposits in the brain, and depression. Repeated head impacts elevate tau protein levels causing neural breakdown. The physical blow to the head could directly cause neuron death or breakage of neuron connections. Lesions in neural tissue could release harmful biochemical agents.

Concussions often go unreported, especially at the amateur level. This study highlights the importance of monitoring the accumulation of concussions. Other studies have found that concussions can lead to negative personality and cognitive changes. Although the dangers of concussions cannot be underscored enough, with regards to this study on concussions in former NFL players there are several limitations. Most significantly, it is likely that there are many lurking variables that this study could not account for. For example, risky behavior that leads to concussions may be favored in those prone to depression. Career-ending concussion accumulation may lead to depression. Nonetheless, the number of concussions suffered is a significant predictor of depression later in life.

Most likely, a positive relationship between concussions and depression would apply across sports, competition levels as well as to the military and other non-athletic instances.

Brain Plasticity through Resistance Training

boy running

A study finds that resistance training generates memory gains in mice greater than those seen in resistance-free endurance training. The biochemical pathway appears to be a neurotrophic factor, BDNF.

 

 

In a recent post on Exercisemed.org, the effects of endurance training on memory was discussed. That paper, released in the spring of 2012, discussed the impact that brain derived neurotrophic factor (BDNF) had on memory in middle aged mice (Running throughout Middle-Age Improves Memory function, Hippocampal Neurogenesis, and BDNF Levels in Female C57BI/6J Mice, 2012; Michael W. Marlatt, et al.). The study found that the release of BDNF through endurance exercise improved the memory of middle-aged, female mice. The mechanism is likely brain plasticity, the ability of neurons to form new connections and pathways. A Japanese study published this month found that mice participating in a high-load resistance training program had an even stronger improvement in memory (Voluntary resistance running with short distance enhances spatial memory related to hippocampal BDNF signaling, 2012. Min Chul Lee, et al.).

The study used running wheels to exercise the mice. The mice were assigned to three groups: a sedentary control group (Sed), voluntary wheel running with no resistance (WR) and voluntary wheel running with increasing resistance.  The mice were maintained with these controls for 30 days. As the figure below shows, the mice with resistance-free running wheels ran a greater distance than their counterparts with resistance running wheels. However, the work performed was higher in the resistance wheel group. Resistance is given as a percentage of body weight.

Screen Shot 2012-10-29 at 3.02.10 PM

The mice were tested for memory capacity and general cognitive function with a water maze. The water maze has a hidden platform that the mice must find.  The mice were placed in the maze four days in a row.  On average, the mice became more efficient at finding the hidden platform each day. As the figure below demonstrates, the mice with running wheels performed better than the sedentary mice (Sed) regardless of whether or not they had resistance (RWR) or no resistance (WR) on their running wheels. The mice that did resistance training spent more time in the target quadrant, quadrant P (graph C).

Screen Shot 2012-10-29 at 3.19.49 PM

Like other studies, the neurotropic factor BDNF was found to be higher in the wheel running groups. In addition, the protein p-CREB was found to be higher in the wheel running groups and significantly higher in the resistance wheel running group. BDNF and p-CREB have both been implicated by previous studies in brain plasticity and memory. The authors speculated that the gains in resistance training were observed because the training was voluntary. Thus, the negative affects of stress on the brain did not occur. This is the first study to suggest that quality over quantity is the rule for brain plasticity.

Exercise’s effect on brain plasticity is a very “hot” research subject right now.  However, no research has been done on the biochemical affects of exercise in human subjects. While other studies have been focused on endurance training’s effect on brain plasticity, this is the first to look at how shorter resistance training affects the brain.

How Exercise Supercharges Your Brain

brainRegular exercise causes long-lasting elevations in the brains basal glycogen levels though the buildup of repeated supercompensation.

Exercise supercharges your brain. According to the latest findings from a Japanese study, exercise results in sustained elevated glycogen levels (Brain glycogen super compensation following exhaustive exercise, 2012, Takashi Matsui, et al.). Glycogen levels have been shown to be elevated in skeletal muscle following exercise, but this is the first study to report of the phenomenon in the brain.

Exercise’s effect on glycogen levels in the skeletal muscle have been known for some time. During exercise, glycogen stores are depleted, but the body returns to an elevated level of glycogen in a process called supercompensation. Supercompensation was first reported in the skeletal muscle in the 1960s.  In the 1980s researchers found that skeletal muscle responds to exercise training by maintaining higher basal levels of glycogen. This adaptation to exercise training lengthens the amount of time the muscle can work before exhaustion.

To study the effects of exercise on glycogen levels in the brain, researchers trained mice for 60 minutes a day, 5 days a week for 3 weeks. At the end of the study glycogen levels were observed in the liver, skeletal muscle and brain. During exhaustive exercise, glycogen levels in the brain dropped 50-60%. Glycogen levels in the liver and skeletal muscle dropped 80-90%. The brain was the first to recover from exercise-induced glycogen depletion by peaking at 6 hours after exercise. This supports the “Selfish Brain Theory”: the brain wins during competition for energy resources within the body. Following supercompensation, the brain returned to pre-exercise glycogen levels about 48 hours after exercise. The skeletal muscle took 48 hours to return to pre-exercise glycogen levels following exercise. A supercompensation peak 24 hours after exercise was recorded in the skeletal muscle. The liver did not show supercompensation and took 48 hours to recover pre-exercsise glycogen levels. These results can be seen in the figure below.

Glycogen levels in the brain, skeletal muscle and liver following exhaustive exercise as a function of time.

More insight was achieved by comparing glycogen levels in the brain between exercise-trained mice and a sedentary control. Glycogen levels in the brain were found to be significantly higher in the exercise-trained mice. The exercise-trained mice were killed 72 hours following the last bout of exercise and their brain tissue was evaluated. The cortex and hippocampus, but not the hypothalamus, brainstem or cerebellum, were found to have significantly higher levels of glycogen than the control. This suggests that supercompensation in the brain results in a long-lasting increase in glycogen levels. The differences in brain glycogen levels between exercise-trained and sedentary control mice can be seen in the figure below.

Glycogen levels in the brain 72 hours after exercise in exercise-trained mice compared with sedentary control mice.

An interesting correlation was found between exercise-induced glycogen depression and the supercompensation that followed. The glycogen depression and supercompensation that followed were positively correlated; that is, a greater glycogen depression results in a stronger glycogen supercompensation in the brain.

Exercising daily causes the brain to have elevated levels of basal glycogen after just three weeks. What are some potential benefits? There are obvious benefits to endurance athletes.  Low sugar levels in the brain are a major source of fatigue. Therefore, elevated glycogen levels would help alleviate onset of fatigue during endurance competition. In addition, increases in glycogen levels have been linked to an increase in cognitive. It has been reported on exercismed.org that students who exercise demonstrate better academic performance (See Lifestyle Impact on Academic Performance). Could the glycogen that supercharges their brain be the biological mechanism?

Exercise is the supercharger of brains.

Exercise versus Anti-Depressant Medication

depressed girl

Exercise has been shown to be comparable in remission rate and adherence rate to anti-depressant medication. However, exercise does not have the social stigma that prevents many from seeking anti-depressant medication.

 

Mild to moderate major depressive disorder (MDD) is a serious illness that affects many Americans. According to the Global Burden of Disease, MDD ranks second globally, only behind heart disease, in responsibility for years of life lost due to disability or premature death. According to a 1999 report from the US Surgeon General, only 23% of people inflicted with MDD seek treatment. Unfortunately, the social stigma around depression, and psychological problems in general, prevents many people from seeking treatment. This stigma is a major hurdle to getting proven pharmaceutical anti-depressant treatments out to those who need them. A small, carefully controlled study found that exercise, an activity viewed positively by society, may work as well as anti-depressant pharmaceuticals and better than cognitive therapy in curing mild to moderate major depressive disorder (Exercise treatment for depression: Efficacy and dose response (2004)).

The study, published in 2005 in the American Journal of Preventive Medicine, divided study participants with MDD into 4 experimental groups and a control group. The experimental group was separated by dosage of exercise and frequency by which that dosage was administered. The exercise dosages were the public health recommended 17.5 Cal/kg/week and a low dosage of exercise at 7.0 Cal/kg/week. The frequency by which these dosages were administered was 3 times a week and 5 times a week. The control group participated in flexibility exercise 3 days a week.

Interestingly, the frequency of exercise per a week did not affect the success of the treatment. However, dosage of exercise did.  Although the public health recommended dosage of 17.5 Cal/kg/week had a success rate (47% reduction in 17-item Hamilton Rating Scale for Depression-HRSD) comparable to pharmaceutical anti-depressants, the low exercise dosage of 7.0 Cal/kg/week resulted in a success rate (30% HRSD reduction) only slightly better than the placebo (29% HRSD reduction). The results of the different dosages are shown in the figure below.

The study administered exercise dosage in a clinically controlled, individual setting to ensure validity of dosage and exclude social benefits of exercising with others. The treatments were administered for 12 weeks.

Remission rate of depression symptoms by the public health recommended exercise dose was 42%. This compares to a 42% remission rate of anti-depressant medication imipramine hydrochloride and a 36% rate of remission for cognitive behavioral therapy (R.R. Pate, M. Pratt, S.N. Blair et al. Physical activity and public health. 1995). In addition, exercise treatment has been criticized for treatment adherence. However, in this study the exercise treatment adherence (72%) compares favorably to adherence rates found in medication trials.

In summary, the public health recommended dosage of exercise treats depression as well as anti-depressant medication. However, low dosage of exercise did little better than the placebo control group. Frequency did not affect the results. Adherence rate was comparable to medication trials suggesting it could provide a viable, stigma-free alternate treatment. This study was small by many standards, 80 participants, but more research should be done to explore the alternate treatment of mild or moderate major depression disorder with exercise.