Tag Archives: Meryl Streep

The origin of runner’s high

There is a great moment (for the neuropharmacologist) in “Postcards from the Edge” with Meryl Streep.  She’s walking along with the bimbo who she just found out seduced the guy who seduced her, when the bimbo blurts out that she feels great because of her endolphins.

Well exercise may raise endorphins in the blood which many regarded as an explanation of the runner’s high.   But almost as soon as the endorphins were discovered, it was found that they don’t get into the brain when injected into the blood.   (If you’re wondering how we can know this, it is based on a synthetic endorphin containing a radioactive atom — injecting it into the blood stream shows it doesn’t get into the brain.

This shouldn’t be surprising, the brain is quite selective about what it lets in.  Consider the first useful treatment of Parkinson’s disease, L-DOPA (L DihydrOxy PhenylAlanine) which does get into the brain, which then breaks it down to dopamine losing two oxygens in the process, which doesn’t get into the brain (even though dopamine is a smaller and less complicated molecule).   Functionally, this is known as the blood brain barrier (BBB).

So maybe exercise raises endorphrins in the brain, but a better explanation for the runner’s high is now at hand [ Nature vol. 612 pp. 633 – 634, 739 – 747 ’22 ].  You won’t believe the answer, which involves the organisms in your gut, but the evidence is quite good, as you are about to read.

First, the composition of the gut microbiome predicts how much mice voluntarily run on exercise wheels or treatmills.  Treatment with antibiotics which diminishes the amount of microbiota diminishes exercise endurance.  Adding the gut microbiome from high exercise mice to germ free mice (gnotobiotic mice) raises running capacity to that of the donor.

Increased levels of dopamine are considered rewarding or pleasurable.  Cocaine prevents it from being taken up after neurons release it, an antidepressant (Monamine Oxidase — MAO) prevents it from being destroyed. etc. etc.

It is known that exercise increases the levels of dopamine in an area of the brain called the striatum.  Dopamine gets to the striatum by the axons of neurons in the ventral tegmental area (VTA).  Inhibition of neurons in the VTA decreases dopamine in the striatum and decreases the amount of exercise a mouse will do.

What does the gut microbiota have to do with this?

Well, germfree (gnotobiotic) mice didn’t change MAO levels in the striatum on exercise, and the dopamine surge and striatal neural activity were blunted.  And germfree mice don’t run as much.

Well, clearly the little bugs down there are producing some sort of signal which IS getting to the brain, not an easy feat getting past the blood brain barrier given the example of L-DOPA above.

We know the bugs produce all sorts of metabolites, the body uses.  One example is vitamin K, which is crucial in the biochemical maturation of coagulation factors, deficiencies of which produce hemorrhagic disease of the newborn. This may explain why the ritual circumcision of Jewish males occurs 8 days after birth, after the gut bacteria have had a chance to make it.

The work cited above shows that the bugs produce fatty acid amides (FAAs) which bind to the type I cannabinoid receptor (CB1) which binds marihuana.

Like just about everything else in the body, there are sensory nerves from the gut going to the spinal cord.  The FAAs activate some of these nerves by binding to CB1.   Giving FAAs to germfree mice increases physical activity.

Gut sensory nerves containing CB1 also have another protein called TRPV1.  Stimulating these nerves with a TRPV1 ligand increases physical activity.  This is true even in germfree mice.

Well we know marihuana has no trouble getting pCast the BBB, so why couldn’t the FAAs produced by the bugs do the same and increase exercise.   Well, it could but it doesn’t.  Severing the sensory nerve before it gets to the spinal cord abolishes the effects of the microbiome (which is still there) on exercise.

So, clearly the continuity of the nerve is crucial for the effect of gut bacteria on exercise, as are FAAs and the CB1 receptor found on the nerve.

Well the sensory nerve from the gut gets into the spinal cord, but there is a lot more work to be done, to determine the pathway by which stimulation of the nerve changes MAO levels in the striatum (as the striatum is a long way from the spinal cord).   So like all great experiments, it suggests further questions and work required to resolve them.

A  beautiful series of experiments.  Could brain ‘endolphins’ still play a role in exercise.  Sure,  but whether they do or not, doesn’t detract from the work here.

One could study the effect of exercise on brain (not blood) endorphins and the effect of cutting the sensory nerve from the gut on their brain levels.




Book recommendation

“It’s complicated”.  No this isn’t about the movie with Meryl Streep but the response I got from several Harvard PhD physicists five years ago at Graduate Alumni Day in April 2014.  A month earlier the BICEP2 experiment claimed to have seen B-mode polarization in the cosmic background radiation, which would have been observational proof of cosmic inflation.  Nobel prize material for sure.  Unfortunately the signal turned out to be from dust in our galaxy, the milky way

You can read all about it in “Losing the Nobel Prize” by Brian Keating, who developed the instrumentation for BICEP2.  I recommend the book for several reasons.  The main reason is the discussion of cosmology and its various theories starting with Galileo (p. 28) getting up to  the B-Modes that BICEPs thought it saw by p. 138.  The discussion is incredibly clear, with discussions (to name a few) of how Galileo knew Ptolemy was wrong (the way the moons of Jupiter moved around it in time), refracting vs.reflecting telescopes, Hubble and cepheid variables, Vera Rubin and why she didn’t get a Nobel — she died too soon, how polaroid glasses work, and why bouncing of water is enough to polarize unpolarized light.  Want more? Fred Hoyle and steady state cosmology, the problems with the big bang (smoothness problem, horizon problem, flatness problem) solved by Alan Guth and inflation, false vacuum, and finally what B-modes actually are.

If you’ve a typical reader of blogs scientific but not a pro in physics, astronomy, cosmology, you’ve probably heard all these terms. Keating explains them clearly.

Even better, he writes well and is funny.  Here is the opening paragraph of the book.

“Each year, on December tenth, thousands of worshippers convene in Scandinavia to commemorate the passing of an arms dealer known as the merchant of death.  The eschatological ritual features all the rites and incantations befitting a pharaoh’s funeral.  Haunting dirges play as the worshippers, bedecked in mandatory regalia, mourn the merchant.  He is eerily present; his visage looms over the congregants as they feast on exotic game, surrounded by fresh-cut flowers imported from the merchant’s mausoleum.  The event culminates with the presentation of gilded, graven images bearing his likeness.”

Anything dealing with the creation of the universe has theological overtones, and we can regard the book as a history of various scientific creation myths, the difference being that they are abandoned when evidence is found which contradicts them.  Georges’ Lemaitre, a catholic priest and relativist puts in more than an appearance (p. 56) as he predicted what is probably the first big bang theory — the primeval atom with its subsequent expansion.

The book isn’t all science, and the author whose Jewish father abandoned them was raised by a catholic step-father describes being an altar boy for a time.   Then there are adventure stories of journeys to the south pole for the BICEP experiment.

There’s a lot more in the book, which is definitely worth a read.

Finally a few personal notes.  The man who brought BICEP2 down to earth David Spergel appears.  He’s a good guy.  At my 50th reunion there my wife and I  were standing in our reunion suits outside our hotel across route 1 waiting for a bus to take us across.  Some guy (Spergel) sees us an offers a ride to campus. On the ride over I asked what he did, and he says astronomy and physics.  So I asked how come the universe is said to be homogenous when all we see is clumpy galaxies and stars — you asked the right guy saith Spergel, and he launches into an explanation (which I’ve forgotten).  I mention that Jim Hartle is a class member.  “He’s very smart” saith David.  Later I tell Hartle the same story.  “He’s very smart” saith Jim.

Another good person is Meryl Streep.  A cousin is in movies both acting in the past and now directing and knows her.  Her father was a great admirer, so Meryl took the trouble to hike over to New Jersey and say hello.  She didn’t have to do that.  Unfortunately in the movie mentioned first, Meryl had to play a porn star with her aged scrawny body (probably Harvey Weinstein put her up to it).  I couldn’t stand it and walked out at that point.

At the Alumni Day

‘It’s Complicated’. No this isn’t about the movie where Meryl Streep made a feeble attempt to be a porn star. It’s what I heard from a bunch of Harvard PhD physicists who had listened to John Kovac talk about the BICEP2 experiment a day earlier. I had figured as a humble chemist that if anyone would understand why polarized light from the Cosmic Background Radiation would occur in pinwheels they would. But all the ones I talked to admitted that they didn’t.

The experiment is huge for physics and several articles explain why this is so [ Science vol. 343 pp. 1296 – 1297m vol. 344 pp. 19 – 20 ’14, Nature vol. 507 pp. 281 – 283 ’14 ]. BICEP2 provided strong evidence for gravitational waves, cosmic inflation, and the existence of a quantum theory of gravity (assuming it holds up and something called SPIDER confirms it next year). The nice thing about the experiment is that it found something predicted by theory years ago. This is the way Science is supposed to operate. Contrast this with the climate models which have been totally unable to predict the more than decade of unchanged mean global temperature that we are currently experiencing.

Well we know gravity can affect light — this was the spectacular experimental conformation of General Relativity by Eddington nearly a century ago. But how quantum fluctuations in the gravitational field lead to gravitational waves, and how these waves lead to the polarization of the background electromagnetic radiation occurring in pinwheels is a mystery to me and a bunch of physicists had more high powered than I’ll ever be. If someone can explain this, please write a comment. The articles cited above are very good to explain context and significance, but they don’t even try to explain why the data looks the way it does.

The opening talk was about terrorism, and what had been learned about it by studying worldwide governmental responses to a variety of terrorist organizations (Baader Meinhof, Shining Path, Red Brigades). The speaker thought our response to 9/11 was irrational — refusing to fly when driving is clearly more dangerous etc. etc. It was the typical arrogance of the intelligent, who cannot comprehend why everyone does not think the way they do.

I thought it was remarkable that a sociologist would essentially deprecate the way people think about risk. I’m sure that many in the room were against any form of nuclear power, despite its safety compared to everything else and absent carbon footprint.

Addendum 7 April — The comment by Handles and link he provided is quite helpful, although I still don’t understand it as well as I’d like. Here’s the link https://medium.com/p/25c5d719187b