-----Oorspronkelijk bericht-----
Van: Phil Tompkins <[log in to unmask]>
Aan: [log in to unmask] <[log in to unmask]>
Datum: donderdag 17 juni 1999 5:59
Onderwerp: The Brain in the Gut and PD (long)
The Brain in the Gut and Parkinson's Disease
Parkinson's disease (PD) is commonly defined as a degeneration of
dopamine-producing neurons in the substantia nigra resulting in the
primary symptoms of resting tremor, stiffness, bradykinesia, and poor
balance. But there are numerous other symptoms of PD that seem
remotely, if at all, related to the substantia nigra. These include
such diverse phenomena as slowed emptying of the stomach contents
into the small intestine, sexual impotence, sweating, and seborrhea.
One may well wonder by what mechanism a deficiency of dopamine in the
substantia nigra results in some of these other symptoms.
Dopamine is produced and used elsewhere in the body besides in the
substantia nigra. One such site is a vast neural network embedded in
the gastrointestinal tract known as the enteric nervous system (ENS).
It is becoming evident that the effects of PD on the involuntary
functions of the gastrointestinal system are associated with
degeneration of those dopamine-producing cells located not in the
substantia nigra but rather in the ENS. The mechanism by which these
effects are produced is unknown. However, evidence such as Lewy
bodies in the enteric neurons and loss of dopaminergic neurons in the
colon points to the involvement of the ENS in PD in a manner
analogous to the involvement of the brain in PD.
Gastrointestinal effects of PD attributable to the enteric system's
involvement in the disease include reflux, delayed gastric
emptying, and decreased motility. Swallowing difficulties and
constipation, which have aspects falling under both voluntary and
involuntary control, may be the result of PD in both the brain and
the ENS.
The ENS is located in the muscle and connective tissues that line
the digestive organs. It contains some 100 million nerves cells,
about the same number as are in the spinal chord. Many of its
structures and chemicals parallel those of the brain, which it
closely resembles at the cellular level. It has sensory and motor
neurons, supportive glial cells, information processing circuits
which transmit and process messages, and immune system cells. It
has nearly every major substance found in the brain, including all
the major neurotransmitters. Because of these resemblances, the
ENS has been called a second brain, or "the brain in the gut."
The ENS performs two major functions. First, it regulates the
routine activity of the digestive system, by controlling the
muscles which grind food in the stomach and move it through the
digestive tract; and it regulates secretions which occur in
the digestive tract. A particlar example of a control mechanism is
the feedback loop via which detection of fat in the small intestine
prolongs retention in the stomach of its remaining contents.
In its routine digestive role the ENS can operate quite
independently of the central nervous system, being only fine-tuned
by signals from the latter.
The other major ENS function is to assist in preparing the organism
for facing danger. Upon receipt of a "fight or flight" signal from
the brain via the vagus nerve, the ENS activates "canned" programs
to empty the digestive system by vomiting or diarrhea and to
mobilize an immune mechanism to fight infection.
I take the similarities between the ENS and the brain plus the
relative independence of the ENS to be further reasons to attribute
gastrointestinal PD symptoms to direct involvement of the ENS in
the disease.
The study of Parkinson's disease as it relates to the enteric nervous
system is relatively new. There is some research in this area, but
it has not yet yielded information or drugs for managing
gastrointestinal PD symptoms. Swallowing difficulties and
constipation in PD are handled in basically the same way as they are
for people without PD. Sinemet, the principal PD drug, was designed
to deliver levodopa across the brain-blood barrier to the brain, not
to the ENS. Effects of PD drugs on the ENS are largely unknown.
Hopefully more research will be done. The NIH has increased
funding to the new field of neurogastroenterology, and the NPF has
also provided funds. At least PD can no longer be thought of as a
disorder eminating from the central nervous system alone.
Bibliography
Lewis, Ricki. "Neurogastroenterologists Combine Old And New
Research Approaches." The Scientist, Vol 10, #10, pp. 13-14. May
13, 1996. On-line at
http://www.the-scientist.library.upenn.edu/yr1996/may/
research_960513.html.
Quigley, Eamonn M.M. "Gastrointestinal Dysfunction in Parkinson's
Disease." Seminars in Neurology. Vol 16, #3, pp. 245-250.
September 1996.
"Body's 'Second Brain' May Cause Digestive Disorders." The New
York Times, Jan. 23, 1996.
