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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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!
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
For
more information or classroom activities, see:
Monoamine
neurotransmitters –
Exercise
and mood –
Blood
brain barrier –
Endocannabinoids
–
Endorphins
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