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The Second Brain: The Importance of the Digestive Nervous System

Elvis Presley, the ‘King of Rock and Roll’, died of constipation. At the age of just 42, Elvis died in the most spacious and luxurious bathroom of his home in Memphis, Tennessee. An autopsy revealed that his large intestine was abnormally enlarged.

Patients with Hirschspsrung’s disease, in which nerve cells do not reach part or all of the large intestine during development, have difficulty expelling stool out of the body. This is due to a disruption in colonic peristalsis. Water is lost from the stool that stops at the end of the large intestine, leading directly to constipation.

Nerve cells derived from the neural crest, known as the fourth germ layer, following the inner and outer mesoderm, must establish themselves from the esophagus to the end of the large intestine and function in order for ‘eating and eating’ to proceed smoothly. No one knows where and in what condition the food they swallowed is in their mouth. From nerve cells exchanging signals to each other, digesting and absorbing food, and disposing of the waste, there is virtually nothing we need to worry about. Physiologists call this digestive nervous system the ‘second brain’ and praise its secret independence.

By nature, the brain is closely related to movement. Sea squirts live a sedentary life by filtering seawater and do not have a brain, which is the central nervous system. But surprisingly, sea squirt larvae that look like tadpoles have a brain. The moment a sea squirt attaches itself to a rock, it immediately digests its brain. This is because there is no longer a need to move the fins. This is evidence that nerve cells are needed to move skeletal muscles. But if we think about it carefully, we have another muscle. It is smooth muscle. It is a muscle that continuously moves the 8m long digestive system that runs through the middle of our body. The nervous system is also needed to move these smooth muscles. Hydra, which does not have a central nervous system such as a brain, and sea squirts that have abandoned their brains also have a digestive nervous system. Hydra, which appeared about 650 million years ago, has a neural network and moves the muscle layer of the digestive tract by exchanging signals through neurotransmitters.

In that way, Hydra expels the waste out of the body in about 6 to 9 hours after eating microorganisms in the water. When nerve cells are destroyed by treatment with a toxic substance called colchicine, the hydra’s digestive system becomes almost motionless and cannot push or shuffle its prey.

Multicellular animals, which evolved a digestive nervous system long before the central nervous system, also synthesized a variety of neurotransmitters. Echinoderms such as hydra, sea urchins, and starfish also produce serotonin. This is the same compound known as the happiness hormone. When the amount of serotonin in the brain decreases, humans suffer from depression. In this context, it seems that serotonin should be produced primarily in the brain.

But that’s not the case. More than 90% of the serotonin produced in our body is synthesized in the digestive system like a hydra. What on earth does serotonin, which has been preserved for a long time in the animal kingdom, regardless of vertebrates and invertebrates, do in the digestive system?

As you might guess, serotonin regulates the digestive nervous system and immune response and helps keep intestinal epithelial cells healthy. Patients suffering from inflammatory bowel disease have reduced intestinal bacterial diversity and disrupted serotonin metabolism. As always, these interactions in the digestive system do not proceed in only one direction. To a lesser extent, bacteria also produce serotonin and regulate intestinal metabolites so that the intestines can produce more of this compound. This fact is also evidenced by the lack of serotonin in mice raised under germ-free conditions. The recently discovered new role of serotonin easily extends beyond the digestive system. Platelets send a significant amount of serotonin into the blood throughout the body to regenerate bones or regulate metabolic homeostasis. However, it cannot pass through the brain-blood barrier. Serotonin in the brain and the digestive system work in different places.

Early animals that appeared before the Cambrian period made neurotransmitters such as oxytocin and vasopressin in addition to serotonin. Since these substances were also found in the central nervous system and it was found that neurogenesis and cell types were similar, it was speculated that the primitive nervous system may have developed into the digestive nerves or brain, but no clear conclusion was reached. But one thing is certain. It is true that the digestive nervous system appeared in the animal kingdom before the brain. Eating and packing is truly a core business at the center of the human body, involving active movements of the nervous system and muscles, and the control and cooperation of bacteria. Behind the bulky skeletal muscles that appear before our eyes, there are smooth muscles of the digestive system that move in one direction without any hesitation.

Hongpyo Kim, Professor, College of Pharmacy, Ajou University

2023-10-04 11:27:00

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