As Many Exceptions As Rules: exercise

Showing posts with label exercise. Show all posts

Wednesday, January 20, 2016

Pump Up Your Brain

Biology concepts – learning, memory, attention, concentration, hippocampus, neurotransmitters, neurotrophins, executive function, processing speed, exercise

Many people exercise because of how it makes them feel,

or just because they think it helps them think more

clearly - maybe by reducing stress. They will be happy to

know that exercise actually increases the power of your

brain, everything from learning, to memory, to attention,

to decision making speed.

Many years ago, my father told me the story of how he studied while in college. He would hit the books in a solitary, silent room and just cram until he couldn’t concentrate anymore. Then he would get up, go outside, and run laps around his dorm for a while. Then he would come back and start again. Study, run, repeat. Turns out, the running makes a true difference. Exercise can actually make you smarter!

In a study from 2011, researchers took overweight kids and had them start exercising. Those that had at least 30 minutes of physical activity each day showed increased hippocampus size, and significant improvement on a CAS planning test, an alternative to the standard IQ test.

Planning basically means that their executive function (planning, reasoning, and decision making skills) had improved markedly. They also performed much higher on a math test, even though no additional math instruction had been given.

Exercise has impacts on memory, learning, attention, concentration, and processing speed. So now we know what we are talking about when we say exercise helps learning. Oh – you won’t just take my word that exercising helps? Good, always ask for evidence.

Let’s look at studies just from 2013, although there are many older studies. One study found that a single bout of moderate exercise allowed participants to more accurately complete a test on memory, reason, and planning - and it took them less time. Another study indicated that exercise reduced the loss of cognitive function in middle-aged women. Yet another publication talked about how master athletes (over 50), have a larger brain volume and better cognitive function as compared to their sedentary counterparts.

We can go on. Exercise has been shown to support the cellular structure of the white matter (myelinated) neurons of the cerebral cortex in patients with vascular disease, important for higher thinking functions. And another study shows that processing speed is increased after starting a regular regimen of cardiovascular activity.

The upper image shows where the hippocampus is located

within the brain. There are two, one in each hemisphere.

They are connected as well. The lower image shows the

regions of the hippocampus, including the dentate gyrus

(DG) the area where much of the neurogenesis after

exercise is found.

Finally, we will mention just one of the many 2010 studies. Nine-ten year old kids that exercised regularly had 12% larger hippocampi (plural of hippocampus, part of brain for learning and memory). They were faster on recall tests and they learned new information faster.

So now that you are convinced that exercise does help cognitive functions, the question still remains as to how exercise carries out this miracle. The first thing to get clear is the difference between memory and learning. It might seem that they are the same thing; you have some experience, either verbal, aural, visual, etc. and if you remember it, then you have learned it. But there are subtle differences.

Specialists define learning as a process that will modify a subsequent behavior. Memory, on the other hand, is the ability to remember past experiences. Memory is the record left by a learning process, so you need to have memory to learn. You learn to play piano by studying the notes and the instrument, but you then play it by using your memory to retrieve the notes and fingering that you have learned.

Back to the mechanisms of how exercise help memory and learning. The easy explanation is that exercise helps you sleep, improves your mood, and drives more oxygen to the brain. These undoubtedly help you study better or even notice more that can be used to build knowledge. These are the factors my dad counted on when he went running. But there’s much more.

The hippocampus is important for learning and memory. Many studies of exercise and cognitive function have shown increases in the size of this part of the brain in exercise participants. Those kids that increased their “IQ,” they had an increased hippocampus. So did mice from studies in the 1990’s.

Neurogenesis is the production of new neural cells from

stem cells. There are stem cells located in the brain. They

can become any type of brain cell, depending on stimuli in

the local area. Normally, only a small percentage of

stimulated stem cells will become neurons, but after

exercise the number that survive goes up dramatically.

Exercise upregulates neurogenesis, oxygenation, synaptic plasticity, neurotransmitter populations, myelination, processing speed, and long-term potentiation (LTP). O.K., that’s a lot of big words, so let’s take them one at a time. Remember that all these things are linked together. Plasticity, neurogenesis, and LTP apply to memory. Neurogenesis and processing speed apply to new learning and executive function. Neurotransmitters, plasticity and oxygenation combine to affect attention.

Neurogenesis

A lot of the benefits from cardiovascular exercise come through the making of new neurons (neurogenesis). Yep, this is a huge exception to the rule that central nervous system neurons last your entire life and can’t be recovered or new ones produced. Neurogenesis is how the hippocampi of all those exercisers got bigger.

Regular exercise induces neurogenesis through action of brain chemicals, trophins and NTs. We talked about brain-derived neurotrophic factor (BDNF) 2 weeks ago with respect to mood and we said we revisit this factor. This neurotrophin actually stimulates your brain to make new neurons! More neurons means more connections, and more potential learning.

For most all of the cognitive functions, the lynchpin seems to be BDNF. How does exercise increase BDNF? We aren’t sure yet. It may be that exercise is a stress, this increases the calcium flowing into the brain. The calcium activates many transcription factors, and BDNF is known to require calcium for transcription.

But nothing is ever simple. It is probable that serotonin, IGF-1, and BDNF are all needed to increase neurogenesis in the hippocampus. Inhibitors of any one of these drastically reduce the amount of exercise-induced neurogenesis.

Plasticity

Think of plasticity as a general process, the altering of neurons and their connections. It involves making more neurons (neurogenesis) and the number (developmental plasticity or synaptogenesis) and orientation of the dendritic connections with other neurons (synaptic plasticity).

The images show the increase in the number of dendrites and

possible synaptic junctions over time. The increase in dendrites

is called arborization (arbor = tree) for obvious reasons. The

increase in synapses is called synaptogenesis. Exercise increases

both of these. This image isn’t a result of exercise, but it would

be is similar.

BDNF doesn’t just induce new neuron formation, it can increase the number and size of the connections (synapses) between neurons. IGF-1 is probably involved in this as well, as its main function is to support the growth of fragile, newly formed neurons and connections.

Plasticity is crucial to learning and to memory, since all learning and memory is just a map of connected circuits that work together to access certain information. It is the number and pattern of the connections that determine the amount retained. More connections must help this process.

Long term potentiation

LTP is for memory and learning – the reinforcing of neural connections to make them stronger. Exercise increases LTP, probably through synaptic plasticity, more connections between two neurons would help reinforce each other when they fire. We talked about LTP last year, so read that post and know that exercise increases it.

Unfortunately, for best increases in memory the exercise must be long term. In a 2013 study, neurogenesis was apparent only 14 days after initiation of exercise, and these were immature neurons. LTP wasn’t increased appreciably until 56 days.

Processing speed

Increased speed probably comes through increased IGF-1 and oxygenation, and their effects on the support cells in the brain. Oligodendrocytes and astrocytes help the neurons do their job at peak efficiency. In particular, oligodendrocytes make the myelin sheath that increases transmission speed.

Meet the glial cells. Astrocytes mediate the travel of fluids

and nutrients from the capillaries to the neurons and

between the neurons and the cerebrospinal fluid.

Oligodendrocytes make the myelin sheath around some

axons. Microglial cells are the immune system of the brain,

they phagocytose intruders. Finally, the ependymal cells

line the ventricles in the brain, the spaces that hold the

cerebrospinal fluid.

Astrocytes, on the other hand, are important for blood flow to neurons, and cerebral spinal fluid movement. These two functions would be particularly important for moving neurotrophic factors toward the neurons.

Attention and concentration

Exercise also helps your attention and concentration. And no, these two aren’t exactly the same. They’re more closely related than memory is to learning, but there are still some differences. Both are important for making you smarter, because only by focusing do we take information in – you have to notice something to learn it.

When you are in a room full of people talking, you can still follow the conversation between yourself and one other person. This is one of several different forms of attention. In general, attention is a thinking process for directing and maintaining awareness of stimuli in one’s environment.

Concentration is the ability to control attention for a sustained period. Attention shifts as we wander from thought to thought about different things in our mind or environment, but concentration requires attention to one thing without wandering. In more clinical terms, concentration is a combination of two types of attention; sustained attention and selective attention.

Sustained attention is staying on task, keeping your mind on a single task over time. Selective attention is more about how you pick what you pay attention to. If there are many activities going on within range of your sense, but you focus on one thing and pay no attention to the others, that is selective attention.

Attention span is not equal to sustained attention. It is

focused attention; how long until your brain diverts to

some other stimulus. In 2000, Americans had a 12 second

attention span on average. In 2010, it was down to 8

seconds. Heck, a goldfish has a 9 second attention span,

and we make fun of them!

Attention is centered in the reticular activating system (RAS), near the brain stem. But it connects to other centers that work in attention as well, like the prefrontal cortex and the parietal cortex. The RAS accounts for shifts in levels of awareness to different things. Exercise activates the RAS, which increases alertness, and therefore attention and concentration – my dad was ahead of his time.

It turns out that increased dopamine, serotonin, and norepinephrine in the brain, and particularly the RAS is crucial for attention and concentration. And we talked two weeks ago about how exercise increases all these. In ADHD, they give drugs (methylphenidate) that increase the apparent levels of dopamine. This helps us make sense of studies that show regular exercise alleviates the symptoms of ADD/ADHD.

One last point that I find interesting. The type of exercise seems to make a difference for the increase in neurotrophins. A 2012 study showed that rats that ran on exercise wheels had increased BDNF in the hippocampus, but rats that lifted weights (climbed ladders with weights on their tails) increased only IGF-1. The two proteins work in different pathways, so rat studies show us that it is best to include both aerobic and resistance training in your exercise program. And a rat shall lead them.

Next week, can you die from not getting enough sleep. Yep, and that's not the weirdest part of fatal familial insomnia.

For a good resource on brain structure and function, see the Open College’s interactive brain.

Patten AR, Sickmann H, Hryciw BN, Kucharsky T, Parton R, Kernick A, & Christie BR (2013). Long-term exercise is needed to enhance synaptic plasticity in the hippocampus. Learning & memory (Cold Spring Harbor, N.Y.), 20 (11), 642-7 PMID: 24131795

Cassilhas RC, Lee KS, Fernandes J, Oliveira MG, Tufik S, Meeusen R, & de Mello MT (2012). Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience, 202, 309-17 PMID: 22155655

Davis CL, Tomporowski PD, McDowell JE, Austin BP, Miller PH, Yanasak NE, Allison JD, & Naglieri JA (2011). Exercise improves executive function and achievement and alters brain activation in overweight children: a randomized, controlled trial. Health psychology : official journal of the Division of Health Psychology, American Psychological Association, 30 (1), 91-8 PMID: 21299297

Tam ND (2013). Improvement of Processing Speed in Executive Function Immediately following an Increase in Cardiovascular Activity. Cardiovascular psychiatry and neurology, 2013 PMID: 24187613

For more information or classroom activities, see:

Most of the information for this post comes from recent scientific journals, here is more general information from the internet.

Memory classroom activities –

http://faculty.washington.edu/chudler/chmemory.html

http://www.math.dartmouth.edu/~mqed/eBookshelf/biology/FalseMemoryExperiment.phtml

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=2&ved=0CDMQFjAB&url=http%3A%2F%2Fwww.mrc-cbu.cam.ac.uk%2Fwp-content%2Fuploads%2F2013%2F01%2FWM-classroom-guide.pdf&ei=6qWSUvHkEcmV2QXUoIHwDw&usg=AFQjCNFloXthm7-epm6-sjTh9QnCFbjZ2Q&sig2=RKjw0fLgnl9XOR2YOO3cXg&bvm=bv.56988011,d.aWM

http://teachmag.com/archives/4823

http://www.exploratorium.edu/memory/dont_forget/

http://www.ehow.com/info_7890998_classroom-memory-activities.html

http://psychology.about.com/library/Psychology_Experiments/bl-memory-experiment.htm

http://classroom.synonym.com/memory-chunking-study-activities-5668.html

Hippocampus –

http://www.healthline.com/human-body-maps/hippocampus

https://www.youtube.com/watch?v=YJLHDPTrUYk

http://www.sciencedaily.com/releases/2003/06/030606081111.htm

http://www.wayfinding.net/hippocam.htm

http://scienceoflearning.jhu.edu/research/view/the-cognitive-timeline-the-role-of-the-hippocampus-in-reducing-interference

http://psychology.about.com/od/memory/ss/ten-facts-about-memory_2.htm

http://psychology.about.com/od/hindex/f/hippocampus.htm

BDNF –

http://scientopia.org/blogs/scicurious/2010/12/13/bdnf-and-depression/

http://www.hindawi.com/journals/ijpep/2011/654085/

http://thoughtmedicine.com/2010/05/bdnf-miracle-gro-for-the-brain/

http://www.livestrong.com/article/214646-brain-derived-neurotrophic-factor-exercise/

http://www.huffingtonpost.com/dr-david-perlmutter-md/neurogenesis-what-it-mean_b_777163.html

Neuroglia –

http://apbrwww5.apsu.edu/thompsonj/Anatomy%20&%20Physiology/2010/2010%20Exam%20Reviews/Exam%203%20Review/CH%2011%20Types%20of%20Glial%20Cells.htm

http://faculty.washington.edu/chudler/glia.html

http://blustein.tripod.com/

http://biology.about.com/od/anatomy/a/aa032808a.htm

http://www.youtube.com/watch?v=52NVc9Lku4o

http://training.seer.cancer.gov/brain/tumors/anatomy/neurons.html

Wednesday, January 13, 2016

Exercise Puts Me To Sleep – You Too

Biology concepts – sleep induction, circadian cycle, narcolepsy, insomnia, anterior hypothalamus, neurotransmitters, cytokines, inflammation

Harriet Tubman gained the respect of all after the Civil

War, including that of William Seward, Secretary of State

of the United States (he’s the guy that bought Alaska).

Despite this respect, she ended up penniless. Seward

provided her with a two story brick house in Auburn,

New York where she could live out her days in

relative comfort.

Harriet Tubman was a narcoleptic. No, she didn’t steal things from the Woolworth, that’s kleptomania. She led hundreds of slave to freedom in the years before the American Civil War despite fighting off the urge to go to sleep at any given moment.

Narcolepsy is a sleep disorder that affects 1 in 2000 Americans, and causes them to have episodes of extreme fatigue. They fall asleep at odd times, and are very hard to awaken. In addition, they may also suffer from wakeful dreams, and cataplexy, a condition similar to temporary paralysis. This can’t have instilled confidence in Harriet’s passengers, but she got the job done.

Narcolepsy is basically too much sleep induction, while insomnia is too little. Many people suffer from insomnia, and it can be brought on by many different conditions. Could your New Year’s resolution to start exercising end up helping both narcolepsy and insomnia. Let’s find out.

You wake up in the morning determined to wear yourself out on the treadmill sometime today. You’re going to run to exhaustion in the hopes that you will get a good night’s sleep as a result. Your doctor did say that working out would help you sleep – but is this what he meant? You run until you’re out of energy and then you sleep to refill the gas tank?

Exhaustion from exercise may play a role in inducing sleep, but there’s much more. Exercise helps in insomnia in the elderly according to some reports. Exercise also helps with narcolepsy in children and adults. But how does it help?

There are two competing hypotheses for exercise’s effects on sleep via your brain. They use two different sensors, but they both run through the brain. But first we need to know a little bit more about the sleep center of the brain to explain how exercise is affecting us.

Sleep was the subject of a series of posts a couple of years ago, starting with this post. But we didn’t talk much about the induction of sleep. Sleep used to be considered a passive process; you slept when the stimulatory inputs to the brain were diminished.

Here is the hypothalamus, home of the sleep centers of the

brain. One the left you can see where the hypothalamus is

relative to the rest of the brain structures. On the right is a

cartoon showing the hypothalamus closer, including the

VLPO, the SCN, the LHA for wakefulness, and the MPO

for heat regulation.

Sleep is now known to be an active process, controlled by the anterior hypothalamus and preoptic nucleus. See the picture to help you locate this area of the brain. In the anterior hypothalamus and the preoptic nucleus, stimulation of GABAergic neurons promote sleep induction and maintenance. GABA is a neurotransmitter that is inhibitory, it stops some of neurons from firing. In this case, the neurons it inhibits are the ones that produce orexin/hypocretin. This is another neurotransmitter, but this one stimulates wakefulness.

Orexin is one neurotransmitter with two names. It was discovered by two different groups at just about the same time, and each group named it something different. Scientists haven’t decided yet which name to go with, so they use both.

There are only 10,000-20,000 neurons which produce orexin/hypocretin, so damage to any part of this area of the brain could induce narcolepsy. This may have been what happened to Harriet Tubman after her master hit her in the head when she was 12 years old. On the other hand, the brain trauma may have resulted in too much VLPO and AH sleep promotion. Either way, she was a professional napper.

So stimulating the POAH and the VLPO lead to sleep at least in part by inhibiting the production of orexin/hypocretin. But what stimulates the POAH and VLPO? Knowing nature as you do, you can bet there are several pathways. One way is certainly routed through the circadian clock. We have talked before about the sleep cycle controlled by the clock.

Yet another picture of the brain, this time highlighting the

pineal gland, where melatonin is made. The left side suggests

that light affects the pineal, but it ain’t the way the yellow

arrow shows. The right figure shows the true pathway much

more realistically. The pineolocyte is the cell type found in the

pineal gland. The melatonin is made from tryptophan and

serotonin is an intermediate structure, so you can make it

from serotonin itself.

Different hormones (like melatonin) and neural inputs/outputs stimulate the sleep and wake centers of the brain to create a semi-regular day/night cycle. Many things can mess with the cycle of melatonin and other day/night rhythms, including exercise. Now we can talk about different ways this may occur.

Temperature hypothesis:

The temperature hypothesis for sleep induction states that a one-degree decrease in your core temperature is enough to trigger sleep induction pathways on the brain. How could these two factors be linked? Well, the temperature sensing and regulating centers of your brain are located in the anterior hypothalamus, right next to the sleep centers (POAH and VLPO).

Reducing temperature is a way of saving energy by the body; this is probably an evolutionary holdover from when calories were hard to come by. Decreasing temperature signaled the brain that less activity was going on, so the body induced sleep to further reduce temperature and save energy for the next day.

It so happens that activity also decreases when the sun goes down, or at least it did before Thomas Edison and the electric light. This strengthened the link between temperature and the circadian sleep/wake cycle. To illustrate this point, a 2013 study measured the effects of drugs on both the circadian patterns and temperature. Drugs that altered the light responses in the SCN, including caffeine, also altered core temperature.

GABA (Gamma-aminobutyric acid) is a neurotransmitter

release at the synaptic cleft of some neurons. It is inhibitory

for some wakefulness neurons, so it promotes sleep. On the

other hand, noradrenaline is stimulatory for the orexin

producing neurons so it promotes being awake. In the middle

is adenosine, you know the player in DNA, RNA, and ATP. It

also happens to be a neuromodulatory and can inhibit the

GABA, NA, and orexin neurons.

In the same study, the same responses that reinforced circadian cycle (spontaneous sleep about 16 hours after light stimulation) also reduced the core temperature at the same time. Drugs that inhibited one, stopped the other as well. It would appear that temperature and day/night cycles are very much linked for sleep.

That then brings up the question of how exercise helps you go to sleep just by messing with your temperature. You exercise - you get hot - the blood vessels in your skin dilate and you sweat to dissipate some of the heat. But sweating isn’t 100% effective, your core temperature does go up. After you finish exercising, your temperature goes down slowly over time.

This decrease in temperature is the cue for your body to begin sleep. Your anterior hypothalamic temperature-regulating center can’t tell the difference between this decrease and the decrease brought about by circadian rhythms. So you may get sleepy a few hours after exercising, as your temperature comes down.

So, is right before bed the best time to exercise? Nope. Exercising stimulates your brain and cardiovascular system as well as raises your temperature. Trying to sleep right after exercise will probably be harder than normal, just because you are firing on all cylinders in your brain and heart.

The best time to exercise to help you get to sleep is about five hours or so before you plan on retiring for the evening. Your temperature goes up while exercising, and then will start to drop just about the same time you are ready for bed. This will reinforce the circadian cycles and give you the best shot at good sleep.

Insomnia is found in a number of conditions. It is

becoming a serious problem in the elderly, with people

living longer and unfortunately becoming more sedentary.

Complications are shown in the cartoon. You see that the

effects are varied, including the ability to fight off

disease. Who knew that not sleeping could lead

to diabetes!

The above plan applies to most of us, but perhaps not all of us. Very well-trained athletes might be less affected by the changes in body temperature for sleep induction. One 2013 study looked at exercise time, temperature manipulation and sleep patterns in professional and highly trained amateur cyclists. The results showed that evening exercise had no affect on sleep patterns, even if combined with a cold water dunk after the cycling routine (brrr!). Neither exercise nor exercise + decreasing temperature brought on a decreased time to spontaneous sleep. So – they sleep well because they wear themselves out each day.

Cytokine hypothesis:

The other system that may be important for inducing sleep after exercise is the immune system. Cytokines are chemical messages that influence many different parts of the immune system. They come into play when you have an infection, or cancer, or allergy; basically any insult to your system.

There are many different cytokines, and they perform many different jobs. Certain cytokines can even mediate opposing pathways, depending on the stimulus that starts their production and release. Some promote inflammation (pro-inflammatory) when one specific injury is sense, but inhibit inflammation (anti-inflammatory) if a different insult occurs.

Exercise can be seen as a stress to the body. It can injure muscles; in fact, that's how you build muscle. You tear them down a bit through work, and they grow back bigger and stronger. This is an insult that results in cytokine production and release into the bloodstream. But the more you train, the less of an insult your body registers.

IL-1beta, TNF-alpha and IL-10 are cytokines that have been associated with sleep induction. Plasma levels of IL-1beta are highest just as sleep is induced; this is one of the things controlled by the circadian system. But prolonged IL-1beta or TNF-alpha results in short sleep, and it is easy to wake you up.

Cytokines have big roles in the brain, even if they

act indirectly. Second messengers trigger pro-

inflammatory cytokines through the brainstem

which control fever and other symptoms,

including sleepiness. You think it’s a coincidence

that you sleep more when you’re sick?

On the other hand, IL-10 is anti-inflammatory and is higher with physical training over time. A 2012 study showed that in the elderly with insomnia, moderate training over months resulted in lower IL-1beta, lower TNF-a, and higher IL-10. These were also associated with better sleep patterns.

The neurons of the sleep center are sensitive to pro-inflammatory cytokines; inflammation signals disrupt the restful sleep patterns we are looking for. This involves the pro-inflammatory stimulation of cortisol, the stress hormone, so exercise’s help in sleep may be again related to a reduction of stress effects. This is a complicated system, but the take home message is, more exercise results in less pro-inflammatory cytokine action on the brain.

Chronic fatigue is also linked to high levels of pro-inflammatory cytokines in the brain that are unhooked from the decrease induced by training for some time. In the opposite direction, narcolepsy is aided by exercise, perhaps by reducing the cytokines that would inhibit orexin/hypocretin domination (wakefulness) in the anterior hypothalamus.

A 2007 study showed that in mice that don’t make orexin/hypocretin (have narcoplepsy), running on the wheel helped them stay awake more during the day. Of course, it also led to more episodes of cataplexy, so the story is not complete.

Next week, another brain effect of exercise – it can actually build your brain and make you smarter. Start running before that next AP quiz.

For a good resource on the structures of the brain, see Open College's Interactive Brain map.

Vivanco P, Studholme KM, & Morin LP (2013). Drugs that prevent mouse sleep also block light-induced locomotor suppression, circadian rhythm phase shifts and the drop in core temperature. Neuroscience, 254, 98-109 PMID: 24056197

Robey E, Dawson B, Halson S, Gregson W, King S, Goodman C, & Eastwood P (2013). Effect of evening postexercise cold water immersion on subsequent sleep. Medicine and science in sports and exercise, 45 (7), 1394-402 PMID: 23377833

Santos RV, Viana VA, Boscolo RA, Marques VG, Santana MG, Lira FS, Tufik S, & de Mello MT (2012). Moderate exercise training modulates cytokine profile and sleep in elderly people. Cytokine, 60 (3), 731-5 PMID: 22917967

España RA, McCormack SL, Mochizuki T, & Scammell TE (2007). Running promotes wakefulness and increases cataplexy in orexin knockout mice. Sleep, 30 (11), 1417-25 PMID: 18041476

For more information or classroom activities, see:

Exercise and sleep –

http://health.howstuffworks.com/mental-health/sleep/basics/how-to-fall-asleep1.htm

http://well.blogs.nytimes.com/2013/08/21/how-exercise-can-help-us-sleep-better/?_r=0

http://www.huffingtonpost.com/2013/08/28/benefits-exercise-sleep-science_n_3823526.html

http://blogs.scientificamerican.com/scicurious-brain/2013/08/19/exercise-to-sleep-or-sleep-to-exercise/

http://www.usatoday.com/story/news/nation/2013/08/15/sleep-insomnia-exercise/2655209/

http://www.sleeplikethedead.com/exercise-sleep.html

http://www.futurity.org/exercise-improves-sleep-but-not-overnight/

http://www.babble.com/body-mind/snooze-to-win-exercise-and-sleep/

Narcolepsy –

http://www.sciencedaily.com/releases/2013/07/130703101609.htm

http://faculty.washington.edu/chudler/narco.html

http://www.webmd.com/sleep-disorders/guide/narcolepsy

http://www.mayoclinic.com/health/narcolepsy/DS00345

http://www.sleepfoundation.org/article/sleep-related-problems/narcolepsy-and-sleep

http://psychiatry.stanford.edu/narcolepsy/

http://www.narcolepsynetwork.org/

http://www.youtube.com/watch?v=GmXSJooA6T4

Orexin/hypocretin –

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1279673/

http://www.ncbi.nlm.nih.gov/pubmed/19549926

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=5&sqi=2&ved=0CFAQFjAE&url=http%3A%2F%2Fpsychiatry.stanford.edu%2Fnarcolepsy%2Farticles%2Fbioessays23.pdf&ei=-dyHUsmvEsr5kQe01oGABg&usg=AFQjCNFpU2WFd_VTNCRRC6LN1gwLBSw4AA&sig2=vE3wAj2pIN6-dhBv8d-NbQ

VLPO and sleep –

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=7&ved=0CFUQFjAG&url=http%3A%2F%2Fsitn.hms.harvard.edu%2Fwp-content%2Fuploads%2F2011%2F05%2Fsleep2.pdf&ei=AtyHUpjBJ-LCyQG09YG4BA&usg=AFQjCNFgm2usy0A7rYiikC5TodESJ_Bfvg&sig2=pPFL7aSn6F_tZ0DhbMB3sA&bvm=bv.56643336,d.aWc

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=9&ved=0CGAQFjAI&url=http%3A%2F%2Fwww.stanford.edu%2F~davesv%2FHypothalamic%2520Regulation%2520of%2520Sleep.ppt&ei=AtyHUpjBJ-LCyQG09YG4BA&usg=AFQjCNF4bkDRoHvXE0OnDwgffLfspMRPPg&sig2=xriJ8FfLSl5m2gMFbVEiNA&bvm=bv.56643336,d.aWc

http://neurosciencefigures2012hmb300.wikispaces.com/VLPO+Projections+Schematic+Diagram

http://www.dormivigilia.com/?p=3372

http://books.google.com/books?id=bph8MBn5KhUC&pg=PA597&lpg=PA597&dq=VLPO+sleep&source=bl&ots=ykXzQ7mltb&sig=LksrPoNT6_AwcST5Wg32mhb9WMU&hl=en&sa=X&ei=S9yHUoKVA8vyyAHFq4DYAw&ved=0CG4Q6AEwCTgK#v=onepage&q=VLPO%20sleep&f=false

http://thesavvyinsomniac.com/tag/vlpo/

https://www.inkling.com/read/sleep-disorders-medicine-chokroverty-3rd/chapter-4/figure-4-17

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=21&ved=0CCkQFjAAOBQ&url=http%3A%2F%2Fwww.dana.org%2FWorkArea%2Fdownloadasset.aspx%3Fid%3D32598&ei=k9yHUtKzIueTyQGAkYGgDg&usg=AFQjCNEkLOevBfVL5aED2u8OBmu26BgXnA&sig2=HXM-S0UaS7VorqVBjtlLDA

Wednesday, January 6, 2016

It’s An Exercise Resolution

Biology concepts – exercise, stress, aging, mood, neurotransmitters, monoamines, endocannabinoids, endorphins, blood brain barrier

Exercise is a common New Year’s resolution. You want to

test yourself and gain in body and soul what comes from

accomplishing physical tasks. However, there is such a

thing as biting off more than you can chew. Make small

goals and add length and intensity slowly, so you can

always feel you are improving.

It’s New Year’s resolution time! Last year we talked about how difficult your brain makes it to change a habit and we gave you some strategies to help you succeed. But succeed at what? It’s time to decide on a resolution.

Two of the most popular resolutions are to lose weight and to exercise more. These two can be linked, although they don’t have to be – you could just starve yourself. I don’t think anyone should make a resolution to starve this year, so let’s look in more depth at exercise as a good habit.

There are two major questions to be answered as to a “getting fit” resolution. The first is obvious – why would more exercise be good for me? We all know about how expending more energy than you take in will help you control your weight. So that’s an easy one.

Exercise also helps your health by building muscle, improving flexibility, increasing bone density, and improving both cardiac and pulmonary function. All these changes result in reduced susceptibility to diseases, especially diseases of life style, like diabetes, cardiovascular disease, cancer, and metabolic syndrome.

Those benefits were obvious, but you probably know so more. Exercise may hurt – but it also makes you feel good. Intense physical activity is a powerful mood enhancer, while at the same time reducing the effects of stress on your body. We all know folks who go for a run or go lift when they are stressed. It really does work.

Linked to de-stressing you in the short term is exercise’s effect on reducing the results of stress long term. This kind of stress means time, oxidation, wear and tear, as well as mental stress – basically, aging. Even at a cellular level, exercise may work to impede the signs of aging.

A 2010 study divided stressed women into two groups, those that began exercising and those that did not. After just a three-day exercise period, the population that began exercising showed fewer signs of aging in sample cells taken. Maybe wearing yourself out will let you wear yourself out for many more years.

People, well most people, are happier after they exercise.

Stress relief is a major contributor, I recommend that

anytime things are getting on your nerves, go out for a

brisk walk or get on your bike. The sense of

accomplishment also contributes to making you happier,

but there is so much more.

Unrelated to simply wearing you out, physical activity improves your sleep. This is so true that doctors now prescribe exercise to those suffering from insomnia. We’ll talk more about this in a couple of weeks.

The benefit you may not think of is …….thinking. Exercise actually improves cognitive (from Latin = to know or recognize) function and memory. Your brain may not be a muscle, but it definitely benefits from increasing your physical activity. This will be our subject for next week, just in time for the all the kids to have a new weapon in their arsenal for good grades.

Now for the second question about exercise, and it’s a doozie. How does exercise accomplish all these wonderful things? The effects of exercise on your physical body comes mostly from your innate ability to react to stressors. More work required from muscles results in muscles growing bigger and stronger to meet the demand. This includes your heart –it’s a muscle. No, for these biology stories, let’s focus on the mechanisms at work that affords exercise the ability to affect your brain. It’ll blow your mind.

Today let’s talk about how exercise actually makes your brain – and the rest of you, happier.

The monoamines dopamine and serotonin are intimately

involved in several mental disorders. You can see that

decreases in one lead to different problems than losses of

the other, but when they are both down, you get

depression and a will to eat more. Eating is another, not

so healthy, way of feeling happier.

The major players are neurotransmitters (NTs) and other molecules that can alter brain activity. Things like dopamine, serotonin, and norepinephrine are NTs; endocannabinoids and endorphins work to block negative inputs.

Levels of dopamine, serotonin and sometimes norepinephrine neurotransmitter are reduced in many patients with clinical depression. Each of these NTs is produced from single aromatic (meaning they have a ring structure) amino acids. Serotonin is produced from tryptophan, dopamine is produced from tyrosine, and norepinephrine is made from dopamine.

As such, they are called monoamines (mono = one and amine = amino group from an amino acid). They react with millions of brain cells to induce feelings of happiness and well-being. Having too little leads to depression or other psychiatric problems.

Depression is often treated with drugs called monoamine oxidase inhibitors, since the enzyme monoamine oxidase is responsible for degrading the monoamine NTs once they have been released from neuron to stimulate the next neuron. Less degradation means more activity, so using these drugs is like increasing the serotonin, dopamine, and norepinephrine levels in the brain.

Exercise increases serotonin in the brain, so you feel better about the world and your place in it. The increased brain serotonin may come from blood, a single study showed a decrease in blood serotonin after exercise. On the other hand, maybe exercise increases production of serotonin in the brain. Maybe it’s both.

Dopamine isn’t left out when it comes to exercise. Physical activity increases calcium (Ca²⁺) flow to brain, which is necessary for dopamine production. But just as serotonin can be increased in more than one way, so can dopamine activity. Published results show that moderate exercise increases the number of dopamine receptors on neurons, so more good feeling is possible.

So dopamine and serotonin are increased by exercise and make you happy. How about just decreasing any signals that make you less happy? This is the second major effect of exercise; it decreases pain and stress. This occurs through release of two other types of compounds – endocannabinoids and endorphins.

Cancer and AIDS lead to a wasting syndrome call cachexia.

Here is Robin Gibb after he was diagnosed with advanced

liver cancer. There is loss of fat and muscle as the body

tries to burn anything for fuel. These diseases destroy

appetite and mood, so cannabinoids (marijuana) can be

prescribed to elevate both. Exercise would also help by

stimulating endocannabinoids.

Endocannabionoids such as anandamide (AEA) and 2-arachidonoylglycerol (2-GT) are made from arachidonic acid; they are eicosanoid lipids, and are still another function of the lipids. Endocannabinoids are very similar to phytocannabionoids in cannabis (marijuana); they both act on the same receptors to increase appetite, elevate mood, increase immune activity, and decrease memory. This is why cannabis is used for MS and cancer patients.

A study from 2011 shows that blood endocannabinoids, especially AEA, go up after intense exercise. This increase stimulates production of brain derived neutrophic factor (BDNF) in the brain. BDNF and serotonin have a reciprocal effect; each raises the level of the other (see picture below). BDNF also stimulates neurogenesis (more on this in 2 weeks) which can be important in mood, since 50% of female depressives are seen to have a smaller than normal hypothalamus. The effect of AEA after exercise on long term mood and outlook takes just long enough for neurogenesis to begin.

Endocannabinoids also reduce nociceptive (noci = unpleasant) inputs, so your pain tolerance goes up with exercise. A 2013 study showed that exercise-induced increases in endocannabinoids increased rats tolerance for nociceptive stimuli, either by mechanical means or through heat. This is similar to how endorphins mimic opioids (like morphine) to create analgesia.

Brain derived neurotropic factor (BDNF) plays a central role

in depression. With increased stress you get more cortisol (a

glucocrticoid) which drives down BDNF and this increases

neuron die back and loss. This is why some people have a

reduced hypothalamus during depression. On the right, you

can see the loop by which increased BDNF drives serotonin

production and serotonin then drives BDNF production. Your

brain wants you to be happy.

Endorphins (endo = internal, and orphine is from morphine) are produced in the pituitary and released into the bloodstream. They interact with opioid receptors on neurons to induce analgesia (an = no, and gesia = feeling), just like morphine. Endorphins are released in times of stress or pain in body – you know, like when you try running a few miles.

Together, endocannabinoids and endorphins reduce pain and this improves mood. Runner’s high, that feeling of euphoria that is supposed to come from long intense exercise, is reported to come from endorphin release after glycogen stores have been depleted (out of immediate energy). However, the high, if you ever feel it, might actually come from reducing the stress and pain inputs. In this environment, the increased serotonin and dopamine can have bigger "be happy" effects.

This is all a great theory, but there’s one problem. The blood brain barrier (BBB) doesn’t let much of what’s in the blood into the brain. In most of the body, the junctions between the cells that make of the blood vessels are a little leaky. Many large and electrically charged molecules can get through them into the tissue. This would be bad for the brain, since many bad molecules can be in the blood as well, toxins and such. The BBB is an evolution-produced guard for our big brain.

The blood brain barrier keeps potentially damaging

molecules out of the brain tissue. On the left you see a

typical vessel, with loose junctions between the

endothelial cells that line the vessel. On the right is a

vessel in the brain. It has tight junctions to greatly reduce

the passage of molecules, and is surrounded by the ends

of astrocytes (helper cells in the brain) which also

provide another layer of protection. The only way

anything of size is getting through is to have a

dedicated transporter.

The BBB comes from the physical connections between blood vessel cells being very tight (hence the name tight junctions). Basically, unless you are small and can simply diffuse through the endothelial cells or you have a specific transporter – you ain’t gettin’ in.

How could serotonin endocannabinoids or endorphins in the blood, or calcium for dopamine production have effects on your brain if they can’t get in?

There are two answers. 1) Endocannabinoids and endorphins have some of their effects outside the brain. There are receptors for them in the peripheral system, where the painful stimuli might occur. This would work well for preventing pain and noxious stimulus inputs from getting to the brains.

Bikram hot yoga takes you through many poses for

stretching and stress relief. The sessions take place in a

105˚F room that is also humidified. You sweat like a

dog, if dogs sweat a lot. This increased heat may help

loosen the blood brain barrier so mood altering

molecules can enter, but the vast majority of mood

enhancement takes intense cardiovascular activity,

something not provided by the average yoga class.

2) It seems that exercise temporarily increases the permeability of the BBB, so serotonin from blood, Ca, endocannabinoids, endorphins, even blood levels of BDNF can get to the brain and help you be happy. As proof, a brain protein was found in the blood after exercise in a 2013 study, indicating the BBB was disrupted.

The increased permeability may come from exercise-stimulates angiogenesis (angio = blood vessel, and genesis = birth). New blood vessels are built, but new vessels are leakier. It may also be that exercise produces heat, and studies have shown that heat in the brain makes the BBB leakier. This may be why hot yoga participants seem so happy afterward – ask them ‘cause I’m not trying it.

Next week, how exercise helps you to sleep better. And it isn’t from just wearing you out. Believe it or not, your immune system is involved!

For a good resource on the structures of the brain, see Open College's Interactive Brain map.

Galdino G, Romero TR, Silva JF, Aguiar DC, de Paula AM, Cruz JS, Parrella C, Piscitelli F, Duarte ID, Di Marzo V, & Perez AC (2013). The endocannabinoid system mediates aerobic exercise-induced antinociception in rats. Neuropharmacology, 77C, 313-324 PMID: 24148812

Koh SX, & Lee JK (2013). S100B as a Marker for Brain Damage and Blood-Brain Barrier Disruption Following Exercise. Sports medicine (Auckland, N.Z.) PMID: 24194479

Heyman E, Gamelin FX, Goekint M, Piscitelli F, Roelands B, Leclair E, Di Marzo V, & Meeusen R (2012). Intense exercise increases circulating endocannabinoid and BDNF levels in humans--possible implications for reward and depression. Psychoneuroendocrinology, 37 (6), 844-51 PMID: 22029953

Vučković MG, Li Q, Fisher B, Nacca A, Leahy RM, Walsh JP, Mukherjee J, Williams C, Jakowec MW, Petzinger GM. (2010). Exercise elevates dopamine D2 receptor in a mouse model of Parkinson's disease: in vivo imaging with [¹⁸F]fallypride. Movement Disorders, 25 (16), 2777-2784 DOI: 10.1002/mds.23407

Puterman E, Lin J, Blackburn E, O'Donovan A, Adler N, & Epel E (2010). The power of exercise: buffering the effect of chronic stress on telomere length. PloS one, 5 (5) PMID: 20520771

For more information or classroom activities, see:

Monoamine neurotransmitters –

http://www.baylorhealth.edu/Research/InstitutesCenters/IMD/ResearchTests/Pages/MonoamineNeurotransmitters%28NE,DA,5H-T%29.aspx

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=38&ved=0CGAQFjAHOB4&url=http%3A%2F%2Fwww.public.coe.edu%2F~mbaker%2Fbaker%2Fdrugs%2Fdb%2520lectures%2F~DB09%2520Neurotransmitters%2520-%2520Monoamines.ppt&ei=suiLUo7hJKfO2gWHi4CQBw&usg=AFQjCNFddCPbyrZxtmtSjLNrk_aAyjY3WQ&sig2=ObyQXdYEYRc9Sf6QvV5cEA

http://www.psychologytoday.com/blog/prefrontal-nudity/201110/marshmallows-and-monoamines

http://www.thenakedscientists.com/HTML/articles/article/clairemcloughlincolumn1.htm/

http://neuroscience.uth.tmc.edu/s1/chapter12.html

http://www.ucl.ac.uk/npp/research/scs

http://www.netdoctor.co.uk/diseases/depression/monoamineoxidaseinhibitors_000101.htm

Exercise and mood –

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=1&ved=0CC8QFjAA&url=http%3A%2F%2Fhealthymeals.nal.usda.gov%2Fhsmrs%2FMissouri%2FExtreme_Health_Challenge%2F18.classroom_activity_breaks.pdf&ei=FOeLUtGOHaPO2QXywYCwBA&usg=AFQjCNG4oVsRQNTnBu12pJwGezbXqlvrjg&sig2=vnpeiBnfWqV7U0om-b7lyg

http://www.google.com/url?sa=t&rct=j&q=&esrc=s&source=web&cd=30&ved=0CGMQFjAJOBQ&url=http%3A%2F%2Fsspw.dpi.wi.gov%2Ffiles%2Fsspw%2Fppt%2Fpasas2ndbreaks.ppt&ei=XOeLUoOfCaLV2AXW-4G4Bw&usg=AFQjCNFupOXTcLqS2DoYlNKQ1uncGF6QQQ&sig2=yEF7ITC7wDvq1-nqVlwbRg