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.

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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).

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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.

Heat, the Brain and Fatigue

sun hot heat sweat 

Heat limits athletic performance. The way heat causes fatigue may be through an elevated brain temperature.

 

 

Our bodies do not perform as well in hot conditions. Hyperthermia is when the body gets overheated resulting in a decrease in maximal power output. Most of us have experienced the fatigue that occurs with heat while exercising or during labor. Personal experience tells us that heat creates fatigue, but what is the physiologically basis of this heat-induced fatigue?

Before looking at how heat affects performance it is important to understand fatigue. There is much debate among today’s exercise physiologists about what actually limits performance during maximal-effort exercise. It is a muscles versus brain dissension. Do the muscles tire, signaling fatigue to the brain or does the brain, in an effort to avoid injuring muscle tissue, signal fatigue to the muscles? The idea that the brain is actually responsible for limiting performance was first introduced in the late 19th century, but has not yet been proven.

A hot environment makes it harder for the body to regulate its body temperature during exercise for several reasons. Blood cools off muscle tissue by moving into the body’s core and out to the skin. A hot environment means that the skin is unable to dissipate heat easily due to a reduced temperature gradient. The elevated temperature of the skin also lowers the temperature gradient between the body’s core and skin. During exercise in a hot environment, blood is simultaneously needed to deliver oxygen to the muscles and to thermoregulate by going to the skin. To make matters worse, blood pressure is reduced because water is being lost as sweat. This strain on available blood is why dehydration is so detrimental to athletic performance in hot environments.

One study found that regardless of the temperature of the exterior environment fatigue always sets in at the same core body temperature [Walters, et al. (2000). Exercise in the heat is limited by a critical internal temperature.]. The authors reasoned that a warm environment simply means that the “critical” core body temperature is reached sooner. However, this critical core body temperature theory has been challenged recently by studies showing ways of altering the critical core body temperature. Dopamine and caffeine were both shown to increase the core body temperature that fatigue sets in. Dehydration, on the other hand, lowered the core body temperature at which fatigue set in. Therefore, not only does being dehydrated mean that your body has a harder time regulating its body temperature, but the body temperature at which fatigue comes on is lower.

Force exerted as a function of time and hyperthermia condition. Four electrical stimulations (EL) were done demonstrating that the muscle was capable of greater exertion from the EL than brain stimulation. Hyperthermia had less effect on muscle contraction during electrical stimulation than brain stimulation.

The brain’s ability to regulate its temperature is stressed during exercise. Cerebral metabolism increases during exercise. Yet, the brain must deal with reduced cerebral blood flow because blood is being diverted to active muscles and thermoregulating skin. It is hard to determine if the core body temperature or brain temperature is responsible for fatigue. Because the brain gets arterial blood from the body core their temperatures are closely linked. Thus, a hot body core results in a hot brain. The brain is typically a fifth of a degree Celsius above the core body temperature. One recent study used experimental techniques to selectively heat the brain during exercise (Lars Nybo, 2012. Brain temperature and exercise performance). The results suggest that the brain’s temperature has a significant impact on performance. However, other studies have concluded that the skin’s temperature sensors are responsible for hyperthermia fatigue [Sawka et al. (2012). High skin temperature and hypohydration impair aerobic performance].

In conclusion, it appears that hyperthermia causes fatigue by elevating the brain’s temperature. Much debate still remains regarding the source of fatigue and the role that hyperthermia plays on fatigue. Understanding the way that heat decreases performance will provide avenues for increasing athletic capability in warm environments.

Fat on the Brain

brain shinyFat literally accrues in the brain of mice consuming a diet high in fat. Exercise was unable to reverse the fat accumulation. The consequences of hypothalamic lipid accumulation may include neural dysfunction and problems with brain regulation.

 

Adipocytes are cells whose specific function is to take up fat. However, fat can also be stored in other cells, a process called lipotoxicity. Excessive fat accumulation in non-adipose tissue can lead to cellular dysfunction and in extreme cases, cell death or apoptosis.

The central nervous system can be affected by lipotoxicity. In a study published this month in the Journal of Physiology, fat content in the hypothalamus region of the brain was observed in mice fed a high-fat diet (Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice, 2012, Melissa L Borg, et al.). Fats generally are not a source of fuel for the brain (glucose is the brain’s primary fuel and fat-derived ketone bodies substitute when the body is starved of carbohydrates). Yet, fatty acids can cross the blood-brain barrier and reach the hypothalamus for regulatory purposes. The hypothalamus is the body’s hunger and body weight regulator. In addition to neuronal signals, the hypothalamus receives input from the levels of fatty acids in the cerebral spinal fluid. The hypothalamus has a limited means of oxidizing fatty acids; therefore, high levels of fatty acids result in fat being stored in the hypothalamus.

The study found that a high fat diet resulted in an increased amount of lipotoxicity in the hypothalamus. Surprisingly, exercise did not reduce the amount of lipids in the high fat diet mice. The mice were fed a high fat diet (59% of calories from fat) or low fat diet (5% of calories from fat) for twelve weeks.  Half of the high fat diet mice were exercised six weeks into the study. As the graph below shows, exercise in the high fat diet mice was able to drop most of the added body weight.

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Body weight of mice over a 12 week period as a function of fat content of diet and exercise over the last 6 weeks.

The high fat diet increased a variety of fats in the hypothalamus. Phospholipids, glycerol lipids, saturated fatty acids and monounsaturated fatty acids were all increased in the hypothalamus as a result of a high fat diet. In addition, high fat feeding increased hypothalamic lipid species known to cause insulin resistance. Yet, exercise was unable to reverse the increase in hypothalamus lipids.

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Epididymal fat in the hypothalamus of mice fed a low fat diet, a high fat diet and a high fat diet with a substantial 6 week training program

The figure above demonstrates that a substantial, 6-week exercise program was not able to substantially reduce the hypothalamus lipid content in mice fed a high fat diet. This suggests that the only way to control fat accumulation in the brain is through diet. Since exercise is not a viable means of reversing fat accumulation in the hypothalamus, other means of reducing lipid accumulation, and the harm it may cause to brain regulation, must be sought.

In conclusion, excess lipid accumulation in non-adipose tissue causes cellular dysfunction leading to diseases such as diabetes. Therefore, lipid accumulation in the hypothalamus due to a high fat diet probably harms regulatory processes in the brain. In the study discussed, exercise was found not to reverse hypothalamus lipid accumulation. The fat content of one’s diet should be monitored even in people with a healthy body weight.

Memory Loss, Anxiety Reduction in Middle-Aged Running Mice

 

Running is shown by one study to increase memory, reduce anxiety, raise stability via increased brains levels of neurotrophic factor BDNF.

 

Running has been shown by several studies to increase neurogenesis (proliferation of new neurons) in the brain, specifically the dentate gyrus in the hippocampus. A decrease in neurogenesis later in life has been linked with memory loss.

A recent study looked at the affects of 6 months of running on neurogenesis and chemistry of brain sections as well as behaviors dependent on brain function (Running throughout Middle-Age Improves Memory function, Hippocampal Neurogenesis, and BDNF Levels in Female C57BI/6J Mice, 2012; Michael W. Marlatt, et al.).

The mice were tested for behavioral changes after one month and six months of voluntary running-wheel training. Many behavioral changes were significant only after six months of training. For example, the running mice were significantly better at the Morris water maze after six months of training, but not after one month of training. How does the water maze work?  Mice were placed in a water bath with a target. After finding the target they were placed back in the water bath at a later date. The mice were tracked with a video camera and the amount of time in the target quadrant was recorded. After six months of training the running mice showed significantly more preference for the target quadrant. This suggests that these middle aged running mice had a greater memory retention.

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Time spent in quadrants in the Morris water maze. Only the 6 month running mice spent significantly more time in the target quadrant.

To test for anxiety, mice were placed in an open field an observed. The ratio of time spent in the center of the field to the periphery of the wall was calculated.  Mice that spent more time in the center of the field would be expected to have less anxiety, while mice that spent time hiding along the wall would have more anxiety. The running mice were found to spend more time in the center of the field than their control counterparts at both one month and six months of voluntary exercise training. This supports previous studies showing that running reduces stress and anxiety.

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Falls on a rotarod after 15 seconds in running mice (dark grey) and resting mice (light grey).

The running mice were found to be stronger and better balanced. This was tested with a rotarod. Mice spent 15 seconds on the rotarod and the number of falls were recorded. The running mice fell about a fifth as much as the control mice as the figure above demonstrates.

The researchers then looked at brain sections of the hippocampus to explain the behavioral differences. BrdU (an agent that gets incorporated into the DNA of new nuclei) was used to look for new neurons. Running mice had significantly higher levels of BrdU in the dentate gyrus of the hippocampus. In addition, DCX, a neural marker, was found to be slightly higher after 6 months of voluntary exercise training.  Finally, neurotrophin factor BDNF was measured. BDNF aids in keeping neurons healthy. The running mice had significantly higher levels of BDNF.

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The dentate gyrus with DCX and DAPI immunochemistry.

 

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A: Running mice showed increased levels of neurogenesis marker BrdU B: BrdU co-localized with NeuN neural marker C: DCX in type D neurons D: DCX in type C neurons

In conclusion, this study found that six months of voluntary running raised memory retention, decreased anxiety and increased stability in middle aged mice. The hippocampus was found to have increased levels of neurogenesis, BDNF and DCX.

Muscle Fiber Influence on Motor Neurons

neurons 

 

A team of Harvard researchers found that muscle fibers have retrograde influence on motor neurons.

 

Athletes generally refer to muscle fibers as “fast twitch” and “slow twitch” depending on muscle contraction speed. From slowest to fastest, the muscles are designated type I, IIA, IIX, IIB. Studies have shown that each motor neuron is homogenous for the muscle fibers it operates. Thus, a slow motoneuron would operate a bundle of slow twitch motor muscle fibers.

Muscle fibers can be converted to a different muscle fiber type by attachment to a alternate motoneuron. For example, a slow twitch muscle fiber can be converted to a fast twitch muscle fiber via attachment to a fast motoneuron. The question then becomes can this mechanism operate in reverse?  In other words, can muscle fibers cause the motoneurons to change from fast to slow and vice versa?

This is the question a team of Harvard researchers sought to address (Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motor neurons, 2010, Joe V. Chakkalakal, et al.).

The researchers introduced a novel marker of slow motoneurons, SV2A. Using immunofluorescence staining the researchers could mark slow motoneurons.  Fast twitch muscle fibers were converted to slow twitch muscle fibers using the transcriptional cofactor PGC-1alpha (discussed in this post on smoking). It was found that an increase in slow twitch muscle fibers led to an increase in slow motoneurons. The possible mechanisms by which an increase in slow-twitch muscle fibers (via PGC-1alpha) increases slow motoneurons synaptic connections is shown below.

Three possible mechanisms by which PGC-1alpha can increase the amount of slow motor neuron terminals. This study confirms that the mechanism is conversion.

The increase in slow motoneurons demonstrates that the mechanism increasing slow synaptic connections is the conversion of motoneurons from fast to slow.  Motoneurons ability to undergo conversion suggests that they have some postnatal plasticity. The authors suggest that there may be a combination of prenatal and postnatal determinants of motoneuron type.

The physiology of motoneurons and their relationship with muscle fibers may have interesting ramifications on the way we look at training. Evidently more than muscle fiber type and capillary proliferation are at play during training.

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.