UCLA Neurobiologists Identify Brain Cells That Control Breathing
For the first time, UCLA scientists have identified the small group of brain cells
believed to originate breathing in mammals. Reported in the September issue of Nature
Neuroscience, their discovery could lead researchers to new approaches to addressing
serious health problems, such as sleep apnea and sudden infant death syndrome. In a
previous study, the UCLA team had pinpointed a specific region of brain tissue called the
preBotzinger Complex as the command post for controlling breathing in mammals. Now,
within the region, they distinguished a small group of neurons responsible for issuing the
commands that generate breathing.
"We hypothesized that if these neurons were important, something unusual would happen
to breathing if we destroyed them," said Dr. Jack Feldman, Edith Agnes Plum Professor,
UCLA neurobiology chair and principal investigator. "As it turned out, we were right."
Using a rat model, the UCLA team zeroed in on the roughly 600 neurons less than one
millionth of one percent of the total neurons in an adult rat's brain. The researchers
stained a unique marker on the cells' surfaces to identify and count them. Then they
administered a toxin that targeted the marker to kill just these cells.
The results proved striking in animals that lost more than 80 percent of their neurons.
"These rats' breathing dissolved from a regular, rhythmic pattern into a highly irregular
pattern of breathing frequency and depth," said Dr. Paul Gray, UCLA neurobiologist and
first author. "Equally important, the rats' brains stopped controlling the amounts of
oxygen and carbon dioxide in the bloodstream the whole point of breathing," he said.
While the findings prove the necessary role of these neurons in normal breathing, UCLA
researchers are equally excited by the study's implications for the future.
"Our findings suggest that these neurons may hold the underlying causes of breathing
disorders and offer an excellent target for drugs treating these disorders," Feldman said.
Because mammals' brains are organized in similar ways, Feldman believes that the same
portion of the human brain will likely control breathing as that of rats.
The UCLA team's next step will be to locate the same set of neurons in a human
brainstem and then compare their physiology and function with the neurons of people
with breathing disorders. If his hypothesis proves correct, Feldman may find fewer or
dysfunctional neurons in the brains of people with breathing disorders.
Human Kidney Protein Found That Regulates Heart Contraction
And Blood Pressure
New Haven, Conn. — Researchers at Yale School of Medicine and the VA
Connecticut Healthcare System in West Haven identified a novel human kidney protein
called renalase that regulates both heart contraction and blood pressure; it is a strong
candidate for easily administered treatment of advanced kidney and cardiovascular
disease. Over eight million people in the U.S. have kidney impairment and 500,000 have
end-stage kidney disease (ESRD), for which treatment is often limited to dialysis.
Elevated blood pressure and cardiovascular disease are commonly associated problems.
Renalase is secreted by the kidneys and circulates freely in the bloodstream. Patients with
kidney disease have very low levels of renalase, suggesting that its absence may lead to
the cardiovascular complications found in ESRD.
“This is one of the most exciting findings of kidney metabolism in recent years,” said
Jianchao Xu, M.D., associate research scientist, attending physician and lead author. “It
has immediate implications for therapy.” Like erythropoietin the human renalase protein
could be injected to replace what is lost in kidney disease.
While the kidneys remove waste and extra water from the body and control the balance
of certain chemicals in the blood like sodium, phosphorus and potassium, by regulating
the body water volume, they also have another function. They secrete hormones, like
rennin and erythropoietin, into the blood to regulate blood pressure and red cell
production.
Neurosurgical Technique Relieves Excessive Sweating
CHICAGO --- Forget that adage about how men sweat but women perspire. We
all sweat, and it's a good thing we do. Sweating controls body temperature. As our
temperature rises, the sympathetic nervous system stimulates certain glands in the body,
the exocrine sweat glands, to secrete water to the skin surface, where it cools the body by
evaporation. There are about five million exocrine glands in the human body -- 2 million
in the hands alone, where they also assist grip. Emotional stress also stimulates sweating,
particularly on the palms and forehead and in the armpits. But some people -- about 1
percent of the population -- sweat copiously following mild stimulation or none at all.
They suffer from a disorder called hyperhidrosis, or excessive sweating.
Hyperhidrosis can be an embarrassing and often occupationally debilitating condition that
seems to be more common in people of Asian descent and in some cases may be
hereditary. Its cause is unknown.
Northwestern neurosurgeon Jeffrey S. Schweitzer, M.D., has treated patients with
hyperhidrosis so severe that their palms literally dripped sweat.
"For these patients, it can be impossible to hold a pen, to pick up a sheet of paper without
soaking it or to touch other people," Schweitzer said. "Imagine how upsetting it is to
shake hands with someone and see that person wipe his hands after touching yours. This
is a daily event for patients with hyperhidrosis."
Schweitzer, assistant professor of surgery at Northwestern University Medical School
and a neurosurgeon at Northwestern Memorial Hospital, treats hyperhidrosis by
performing endoscopic surgery to remove the nerves that stimulate the sweat glands in
the palms. The procedure is done through an endoscope inserted through a small opening
in the chest wall. The patient is usually kept overnight in the hospital.
"The risks associated with this surgery are low, and the effect on the patient's self-image
and ability to interact socially can be very gratifying," Schweitzer said.
The procedure is also highly effective, Schweitzer said, with well over 80 percent of
patients showing significant improvement in sweating on the palms.
Fatty Foods Fight Inflammation
"Take two cheeseburgers and call me in the morning," may sound like far-fetched
medical advice. After all, high fat foods can worsen blockages in blood vessels. But a
new study in the October 17 issue of The Journal of Experimental Medicine shows that
high fat foods can, at least in the gut, soothe inflammation. This action may stop immune
cells from attacking food as a foreign invader.
Eating -- particularly eating fat-rich foods -- causes cells in the small intestine to produce
a hormone called cholecystokinin, or CCK.CCK stimulates digestion and gut peristalsis
(the motion that propels food along the digestive tract), and also triggers satiation – the
full feeling that prompts you to stop eating.
The study by Luyer and colleagues shows that fat-induced CCK can also dampen
inflammation in the gut, as rats fed a high-fat diet were protected against lethal bacteriainduced shock whereas those fed a low-fat diet were not. CCK sent signals to the brain
through the vagus nerve, the nerve that provides the electrical regulation for many
internal organs, including the gut and the heart. In response to CCK, vagus nerve endings
in the gut released a neurotransmitter called acetylcholine. Acetylcholine then bound to
proteins on immune cells and turned the cells off.
The authors think this pathway might explain why the immune system doesn't react to
food proteins and normal gut bacteria as if they were foreign invaders. They also suggest
that triggering this fat-driven chain of events in patients might provide a way to reduce
inflammatory complications after surgery.