Mary Jackson asked:

>Karl--do you have any more info. on this?  I had heard that there was a
>relation between the colon and the brain (I forget the details), but I
>think this is the first I've heard of brain-like material in the gut.

Copyright and all rights reserved by the NY Times (keyed in by a friend).

COMPLEX AND HIDDEN BRAIN IN GUT PRODUCES BUTTERFLIES AND VALIUM

New York Times, January 23, 1996; Science Section C-1, C-3

by Sandra Blakeslee

captions to large illustration at beginning of article:

Gut-Brain Highway:  A 2-Way Street:  The gut has a mind of its own,
the enteric nervous system.  Just like the larger brain in the head,
researchers say, this system sends and receives impulses, records
experiences and responds to emotions.  Its nerve cells are bathed and
influenced by the same neurotransmitters.  The gut can upset the brain
just as the brain can upset the gut.

The "brain in the gut" takes the form of two networks of neural
connections in the lining of the gastrointestinal tract, called the
myenteric plexus.  The nerves are highly interconnected and have direct
influence on things like the speed of digestion, the movement and
secretions of the fingerlike mucosa(cilia) that line the intestines and the
contractions of the different kinds of muscle in the gut wall.

Body of article:

        Ever wonder why people get "butterflies" in the stomach before
going on  stage?  Or why an impending job interview can cause an
attack of intestinal cramps?  And why antidepressants targeted for the
brain cause nausea or abdominal upset in millions of people who take
such drugs?
        The reason for these common experiences, scientists say, is that
the body has two brains--the familiar one encased in the skull and a
lesser known but vitally important one found in the human gut.  Like
Siamese twins, the two brains are interconnected; when one gets upset,
the other does, too.
        The gut's brain, known as the enteric nervous system, is located in
sheaths of tissue lining the esophagus, stomach, small intestine and
colon.  Considered a single entity, it is a network of neurons,
neurotransmitters and proteins that zap messages between neurons,
support cells like those found in the brain proper and a complex
circuitry that enables it to act independently, learn, remember and, as
the saying goes, produce gut feelings.
        The brain in the gut plays a major role in human happiness and
misery.  But few people know it exists, said Dr. Michael Gershon, a
professor of anatomy and cell biology at Columbia-Presbyterian
Medical Center in New York. For years, people who had ulcers,
problems swallowing or chronic abdominal pain were told that their
problems were imaginary, emotional, simply all in their head, Dr.
Gershon said.  They were shuttled to psychiatrists for treatment.
        Doctors were right in ascribing these problems to the brain, Dr.
Gershon said, but they blamed the wrong one.  Many gastrointestinal
disorders like colitis and irritable bowel syndrome originate from
problems within the gut's brain, he said.  And the current wisdom is that
most ulcers are caused by a bacterium, not by hidden anger at one's
mother.
        Symptoms stemming from the two brains get confused, Dr.
Gershon said. "Just as the brain can upset the gut, the gut can also
upset the brain" he said.  "If you were chained to the toilet with cramps,
you'd be upset, too."
        Details of how the enteric nervous system mirrors the central
nervous system have been emerging in recent years, said Dr. Gershon,
who is considered one of the founders of a new field of medicine called
neurogastroenterology.
         Nearly every substance that helps run and control the brain has
turned up in the gut, Dr. Gershon said.  Major neurotransmitters like
serotonin, dopamine, glutamate, norepinephrine, and nitric oxide are
there.  Two dozen small brain proteins, called neuropeptides, are in the
gut, as are major cells of the immune system.  Enkephalins, one class of
the body's natural opiates, are in the gut.  And in a finding that stumps
researchers, the gut is a rich sources benzodiazepines -- the family of
psychoactive chemicals that includes such ever popular drugs as Valium
and Xanax.
        In evolutionary terms, it makes sense that the body has two
brains, said Dr. David Wingate, a professor of gastrointestinal science
at the University of London Hospital.  The first nervous systems were
in tubular animals that stuck to rocks and waited for food to pass by,
Dr. Wingate said.  The limbic system is often referred to  as the "reptile
brain."
        As life evolved, animals needed a more complex brain for
finding food and sex and so developed a central nervous system.  But
the gut's nervous system was too important to put inside the newborn
head with  long connections going down to the body, Dr. Wingate said.
Offspring need to eat and digest food at birth.  Therefore, nature seems
to have preserved the enteric nervous system as an independent circuit
inside higher animals.  It is only loosely connected to the central
nervous system and can mostly function alone, without instructions
from topside.
        This is indeed the picture seen by developmental biologists.  A
clump of tissue called the neural crest forms early in embryogenesis,
Dr. Gershon said.  One section turns into the central nervous system.
Another piece migrates to become the enteric nervous system.  Only
later are the two nervous systems connected via a cable called the
vagus nerve.
        Until relatively recently, people thought that the gut's muscles
and sensory nerves were wired directly to the brain and that the brain
controlled the gut through two pathways that increased or decreased
rates of  activity, Dr. Wingate said.  The gut was simply a tube with
simple reflexes.  Trouble is, no one bothered to count the nerve fibers
in the gut.  When they did, he said, they were surprised to find that the
gut contains 100 million neurons -- more than the spinal cord has.  Yet
the vagus nerve only sends a couple of thousand nerve fibers to the gut.
        The brain sends signals to the gut by talking to a small number
of "command neurons," which in turn carry messages up and down the
pike, Dr. Gershon said.  Both command neurons and interneurons are
spread throughout two layers of gut tissue called the myenteric plexus
and the submucosal plexus.  ("Solar plexus" is actually a boxing term
that refers simply to nerves in the abdomen.)  Command neurons
control the pattern of activity in the gut, Dr. Gershon said.  The vagus
nerve only alters the volume by changing its rates of firing.
        The plexuses also contain glial cells that nourish neurons, mast
cells involved in immune responses, and a "blood brain barrier" that
keeps harmful substances away from important neurons, Dr. Gershon
said.  They have sensors for sugar, protein, acidity and other chemical
factors that might monitor the progress of digestion, determining how
the gut mixes and propels its contents.  'It's not a simple pathway," he
said.  "It uses complex integrated circuits not unlike those found in the
brain."
        The gut's brain and the head's brain act the same way when they
are deprived of input from the outside world, Dr. Wingate said.  During
sleep, the head's brain produces 90 minute cycles of slow wave sleep
punctuated by periods of rapid eye movement sleep in which dreams
occur.  During the night, when it has no food, the gut's brain produces
90 minute cycles of slow wave muscle contractions punctuated by short
bursts of rapid muscle movement, Dr. Wingate said.
        The two brains may influence each other while in this state, Dr.
Wingate said.  Patients with bowel problems have been shown to have
abnormal rem sleep.  This finding is not inconsistent with the folk
wisdom that indigestion can produce nightmares.
        As light is shed on the circuitry between the two brains,
researchers are beginning to understand why people act and feel the
way they do.  When the central brain encounters a frightening situation,
it releases stress hormones that prepare the body to fight or flee, Dr.
Gershon said.  The stomach contains many sensory nerves that are
stimulated by this chemical surge -- hence the "butterflies."  On the
battlefield, the higher brain tells the gut brain to shut down, Dr.
Gershon said.  "A frightened, running animal does not stop to
defecate," he said.
        Fear also causes the vagus nerve to "turn up the volume" on
serotonin circuits in the gut, Dr. Gershon said.  Thus overstimulated,
the gut goes into higher gear and diarrhea results.  Similarly, people
sometimes "choke" with emotion.  When nerves in the esophagus are
highly stimulated, people have trouble swallowing.
        Even the so-called "Maalox moment" of advertising fame can be
explained by the two brains interacting, said Dr. Jackie D. Wood,
chairman of the department of physiology at Ohio State University on
Columbus.  Stress signals from the head's brain can alter nerve function
between the stomach and esophagus, resulting in heartburn.
        In  cases of extreme stress, Dr. Wood said, the higher brain
seems to protect the gut by sending signals to immunological mast cells
in the plexus.  the mast cells secrete histamine, prostaglandin and other
agents that help produce inflammation, he said.  "This is protective.  If
an animal is in danger and subject to trauma, dirty stuff in the intestines
is only a few cells away from the rest of the body.  By inflaming the
gut, the brain is priming the gut for surveillance.  If the barrier breaks,
the gut is ready to do repairs," Dr. Wood said.  Unfortunately, the
chemicals that get released also cause diarrhea and cramping.
        Such cross talk also explains many drug interaction, Dr.
Gershon said.  "When you make a drug to have psychic effects on the
brain, it's very likely to have an effect on the gut that your didn't think
about," he said.  Conversely, drugs developed for the brain could have
uses in the gut.
        For example, the gut is loaded with the neurotransmitter
serotonin.  When pressure receptors in the gut's lining are stimulated,
serotonin is released and starts the reflexive motion of peristalsis, Dr.
Gershon said.
        Now a quarter of people taking Prozac or similar
antidepressants have gastrointestinal problems like nausea, diarrhea and
constipation, he said.  These drugs act on serotonin, preventing its
uptake by target cells so that it remains more abundant in the central
nervous system.
        In a study to be published soon, Dr. Gershon and his colleagues
explain Prozac's side effects on the gut.  They mounted a section of a
guinea pig colon on a stand and put a small pellet in the "mouth" end.
The isolated colon whips the pellet down to the "anal" end of the
column, just as it would inside an animal, Dr. Gershon said.
        When the researchers put a small amount of Prozac into the
colon, the pellet "went into high gear," Dr. Gershon said.  The drug
doubled the speed at which the pellet passed through the colon, which
would explain why some people get diarrhea.  Prozac has been used in
small doses to treat chronic constipation, he said.
        But when researchers increased the amount of Prozac in the
guinea pig colon, the pellet stopped moving.  The colon froze up, Dr.
Gershon said, which is why some people get constipated on the drug.
And because Prozac stimulated sensory nerves, he said, it can also
cause nausea.
        Some antibiotics like erythromycin act on gut receptors to
produce oscillations, Dr. Gershon said.  People experience cramps and
nausea.  Drugs like morphine and heroin attach to the gut's opiate
receptors, producing constipation.  Indeed, both brains can be addicted
to opiates.
        Victims of Alzheimer's and Parkinson's diseases suffer from
constipation.  The nerves in their gut are as sick as the nerve cells in
their brains.
        Just as the central brain affects the gut, the gut's brain can talk
back to the head, Dr. Gershon said.  Most of the gut sensations that
enter conscious awareness are negative things like pain and
bloatedness, Dr. Wingate said.  People do not expect to feel anything
good from the gut but that does not mean such signals are absent, he
said.
        Hence, the intriguing question:  why does the human gut
produce benzodiazepine?  The human brain contains receptors for
benzodiazepine, a drug that relieves anxiety, suggesting that the body
produces its own internal source of the drug, said Dr. Anthony Basile, a
neurochemist in the Neuroscience Laboratory at the National Institutes
of Health in Bethesda, Md.  Several years ago, he said, an Italian
scientist made a startling discovery.  Patients with liver failure fall
into a
deep coma.  The coma can be reversed, in minutes, by giving the
patient a drug that blocks benzodiazepine.
        When the liver fails, substances usually broken down by the
liver get to the brain, Dr. Basile said.  Some are bad, like ammonia and
mercaptans, which are "smelly compounds that skunks spray on you,"
he said.  But a series of compounds are also identical to
benzodiazepine.  "We don't know if they come from gut itself, from
bacteria in the gut or from food,"  Dr. Basile said.  But when the liver
fails, the gut's benzodiazepine goes straight to the brain, knocking the
patient unconscious.
        The payoff for exploring gut and head brain interactions is
enormous, Dr. Wood said.  For example, many people are allergic to
certain foods, like shellfish.  This is because mast cells in the gut
mysteriously become sensitized to antigens in the food.  The next time
the antigen shows up in the gut, Dr. Wood said, the mast cells call up a
program, releasing chemical modulators that try to eliminate the threat.
The allergic person gets diarrhea and cramps, he said.
        Many autoimmune diseases like Krohn's disease and ulcerative
colitis may involve the gut's brain, Dr. Wood said.  The consequences
can be horrible, as in Chagas disease, which is caused by a parasite
found in South America.  Those infected develop an autoimmune
response to neurons in their gut, Dr. Wood said.  Their immune
systems slowly destroy their one gut neurons.  When enough neurons
die, the intestines literally explode.
        A big question remains.  Can the gut's brain learn?  Does it
"think" for itself?  Dr. Gershon tells a story about an old Army
sergeant, a male nurse in charge of a group of paraplegics.  With their
lower spinal cords destroyed, the patients would get impacted.
        "The sergeant was anal compulsive," Dr. Gershon said.  "At 10
A.M. everyday, the patients got enemas.  Then the sergeant was
rotated off the ward.  His replacement decided to give enemas only
after compactions occurred.  But at 10 the next morning, everyone on
the ward had a bowel movement at the same time, without enemas,"
Dr. Gershon said.  Had the sergeant trained those colons?
        The human gut has long been seen as a repository of good and
bad feelings.  Perhaps emotional states from the head's brain are
mirrored in the gut's brain, where they are felt by those who pay
attention to them.