Evidence for cellular cause of SIDS found
CHICAGO, March 7 (UPI) -- University of Chicago scientists say they've found
a disturbance of a specific neurochemical might lead to sudden infant death
syndrome. The researchers describe what happens during hypoxia when
levels of the hormone serotonin are disturbed in the specific group of
neurons shown to be responsible for gasping, which resets the normal
breathing pattern for babies.
Sudden infant death syndrome is the primary cause of death before age 1 in
the United States. Approximately 3,000 infants die each year from SIDS,
according to the Centers for Disease Control and Prevention. "This
confirms our previous studies," said lead author Jan-Marino Ramirez, a
professor of organismal biology and anatomy. "Now we've just better defined
the players in the system." In a paper published last year in the journal
Neuron, Ramirez found sodium-driven pacemaker cells controlled gasping. That
work in tissue slices was confirmed in a study published last month by
University of Bristol researchers who found the same results in rats.
The research appears in the March 8 issue of the Journal of Neuroscience.
Reprinted from EarthPuIse Flashpoints, New text Number
Two.
Editors Note: Drs. Patrick and Gael Crystal Flanagan are independent
scientists and researchers. They are regular contributors to the Earthpulse
Flashpoints. Their work is the subject of the book, Towards a New Alchemy:
The Millennium Science.
The most intelligent pharmacist is inside our head. Our brains generate a
complex cocktail of biologically active drugs, hormones and chemicals.
Through the use of diet and other techniques, we can consciously affect the
balance of these materials and their effects on our emotional states. Moods
and behavior are largely influenced by the ratio of five central nervous
system chemicals known as amines. These include: norepinephrine (noradrenaline),
epinephrine (adrenaline), serotonin (5-HT), dopamine and phenylethylamine
(PEA). The first three excite the CNS (central nervous system) while the
last two inhibit or modulate that excitement. The ratio of these amines
controls our levels of irritability.
1. Epinephrine triggers anxiety. (Excitatory)
2. Norepinephrine triggers hostility and irritability. (Excitatory)
3. Serotonin, at increasing levels stimulates nervous tension, drowsiness,
heart palpitations, water retention and inability to concentrate and
perform. (Excitatory)
4. Phenylethylamine is a mood elevator that makes us feel euphoric at low
levels. At higher levels it causes paranoia.
Phenylethylamine is found in chocolate and is considered to be the reason
why many people are chocolate addicts. (Inhibitory)
5. Dopamine modulates or off sets the negative effects of the excitatory
amines by inducing relaxation and mental alertness. (Inhibitory)
So we can see that adequate dopamine and phenylethylamine levels are
extremely important to balance the excitatory amines for enhanced emotional
stability.
We can readily see that an increase in the levels of the first three of
these amines can result in an irritated, agitated state. A person with an
excess of these brain chemicals is easily irritated.
The activity of these amines is largely determined by an enzyme known as MAO
or monamine oxidase. MAO is divided into two types. MAO type A deactivates
epinephrine, norepinephrine and serotonin while MAO type B deactivates
dopamine and PEA (phenylethylamine). An increase in type A MAO and a lower
level of type B MAO is ideal for creation of emotional stability.
The types of food we consume can have a powerful effect on the interplay of
these biological amines. Amino acids from dietary proteins act as precursors
for these activities. For example:
A. L-phenylalanine is a precursor for PEA
(phenylethyla-mine).
B. L-Tyrosine is a precursor for dopamine, norepinephrine and epinephrine.
The conversion of tyrosine to any of these amines is determined by the
amount of magnesium and vitamin B6 in the body. C. L-Tryptophan is a
precursor for Serotonin.
The conversion of all these precursors into their various amines is
controlled by one enzyme. This enzyme is called decarboxylase. The activity
of decarboxylase is greatly affected by the active form vitamin B6. The
vitamin B6 we take in vitamin pills (Pyridoxine Hydrochloride) is inactive
and must be activated before it can be used by the body. Steroid type
hormones also affect the balance of these amines. For example, estrogen and
testosterone suppresses type A MAO while increasing type B activity
therefore increasing the levels of excitatory amines such as adrenaline,
noradrenaline and serotonin.
Progesterone and dihydro-testosterone increases type A activity while
suppressing type B activity therefore decreasing the excitatory amines
therefore increasing biological levels of the modulating amines doparnine
and PEA.
Magnesium and Vitamin B deficiencies cause a reduction in the production of
dopamine. Studies in animals have shown that a magnesium deficiency causes a
depletion of brain dopamine without affecting brain serotonin and
norepinephrine. Active Vitamin B6 increases the cellular absorption of
magnesium and therefore works in concert to increase the production of
dopamine. When we eat a lot of sugar, the body transfers the amino acid
tryptophan from the blood stream into the central nervous system where it is
converted into serotonin. Continued high daily use of sugar can result in a
chronic state of sertonin excess with a dopamine deficiency, resulting in
irritability.
The Ideal State
The ideal state is to have a ratio of amines such that the inhibitory
modulating amines such as dopamine and PEA are in greater abundance than the
exicitatory amines such as adrenaline, noradrenaline and serotonin. This can
be easily accomplished by a change in diet.
Tyrosine can be converted into either excitatory or inhibitory amines.
Vitamin B6 is the key nutrient in the production of the beneficial biogenic
amines dopamine and PEA. As stated previously, Vitamin B6 in the form of
pyridoxine hydrochloride is biologically inactive. In order to activate it,
it must be converted into a chemical known as pyridoxal phosphate (PLP).
This conversion to the active form requires magnesium and riboflavin
(Vitamin B2). Adequate levels of vitamin B6 and magnesium along with the
other B Vitamins will help to insure the conversion of dietary amino acids
into the preferred amines.
Animal fats in the intestine contribute to the formation of bacteria that
stimulate the conversion of inactive estrogen to the active form. Increased
estrogen levels suppress type A MAO and enhance type B MAO causing an
excited neural state. Studies have shown that vegetarian women are far more
stable and have significantly lowered levels of premenstrual tension as
compared with non-vegetarians. The estrogen like activity of insecticides
and chemicals used in plastic manufacture may also be enhanced by this
process. Increased estrogen levels are also associated with increased levels
of cancer.
In general, if a person is suffering from irritability due to an
excitatory/inhibitory biogenic amine imbalance, the following dietary
suggestions should be followed:
1. Serotonin production is increased by higher levels of carbohydrate.
Therefore, carbohydrate intake should be limited to no more than 20% of
total calories.
2. Limit or eliminate dairy products because they tend to suppress the
absorption of dietary magnesium and the animal fat contributes to higher
estrogen levels as explained previously.
3. Eliminate all animal fats and replace with vegetable based fats to no
more than 30% of daily calories.
4. Eliminate or reduce the use of animal proteins as much as possible. Use
vegetable proteins instead.
5. Eat plenty of high fiber foods because higher dietary fiber helps to
eliminate estrogens and precursors from the intestines.
6. Reduce caffeine intake as it is a powerful CNS stimulant.
7. Supplement diet with 1,000 mg per day of magnesium, 100mg per day of
vitamin B6 and take a vitamin supplement that contains the other B Vitamins.
The Brain's Pharmacy
Serotonin's Effects Extend Far Beyond Brain
Neurochemical could play key role in embryonic development, study
suggests
MONDAY, May 9 (HealthDay News) -- The brain chemical serotonin is present
in embryos long before neurons form and plays a role in determining the
position of organs during embryonic development, scientists report. These
findings about serotonin, which is involved in the transmission of
signals between neurons and plays a role in anxiety and mood disorders,
could have a potential impact in many fields, including neuroscience,
developmental genetics, evolutionary biology and human teratology -- a
branch of pathology and embryology that focuses on abnormal development
and congenital malformations, the researchers said.
In work focused on chicken and frog embryos, researchers at the Forsyth
Institute in Boston identified a potential new serotonin-signaling
pathway, offering evidence that the chemical may be able to signal inside
cells. If this signaling also turns up in mammals, including humans, it
could suggest new roles and targets for serotonin-related drugs, the
researchers explained.
"We hope that through better understanding of important but previously
little-studied biophysical signals, new therapeutic applications can be
developed," principal investigator Michael Levin said in a prepared
statement. The study appears in the May 10 issue of the journal Current
Biology.
More information
The U.S. National Library of Medicine has more about fetal development.
-- Robert Preidt http://www.healthday.com/view.cfm?id=525565
SOURCE: Forsyth Institute, news release, May 9, 2005
Serotonin Transporter Gene Promoter Polymorphism And
Autism: A Family-Based
Genetic Association Study In Japanese Population.
http://tinyurl.com/g9nuz
Koishi S, Yamamoto K, Matsumoto H, Koishi S, Enseki Y, Oya A, Asakura A,
Aoki Y, Atsumi M, Iga T, Inomata J, Inoko H, Sasaki T, Nanba E, Kato N,
Ishii T, Yamazaki K.
Department of Psychiatry, Course of Specialized Clinical Science, Tokai
University School of Medicine, Bohseidai, Isehara, Kanagawa 259-1193, Japan.
Autism is now widely accepted as a biological disorder which, by and
large, starts before birth. It has been shown that serotonin (5-HT) is
associated with several psychological processes and hyperserotoninemia is
observed in some autistic patients. The results of previous reports
about family-based association studies between the serotonin transporter
(5-HTT) gene promoter polymorphism and autism are controversial.
In this study, an analysis using the transmission/disequilibrium test (TDT)
between the 5-HTT gene promoter polymorphism and autism in 104 trios, all
ethnically Japanese, showed no significant linkage disequilibrium(P=0.17).
Recently, it has been reported that some haplotypes at the serotonin
transporter locus may be associated with the pathogenesis of autism.
Therefore, further investigations by haplotype analyses are necessary to
confirm the implications of genetic variants of the serotonin transporter in
the etiology of autism. PMID: 16481140 [PubMed - as supplied by publisher]
http://www.nih.gov/news/pr/oct2006/nichd-31.htm
EMBARGOED FOR RELEASE
Tuesday, October 31, 2006
4:00 p.m. ET
CONTACT:
Robert Bock
or Marianne Glass Miller
301-496-5133
SIDS Infants Show Abnormalities In Brain Area Controlling Breathing, Heart
Rate
Serotonin-Using Brain Cells Implicated In Abnormalities
Infants who die of sudden infant death syndrome have abnormalities in the
brainstem, a part of the brain that helps control heart rate, breathing,
blood pressure, temperature and arousal, report researchers funded by the
National Institutes of Health. The finding is the strongest evidence to date
suggesting that innate differences in a specific part of the brain may place
some infants at increased risk for SIDS.
The abnormalities appeared to affect the brainstem's ability to use and
recycle serotonin, a brain chemical which also is used in a number of other
brain areas and plays a role in communications between brain cells.
Serotonin is most well known for its role in regulating mood, but it also
plays a role in regulating vital functions like breathing and blood
pressure.
The study appears in the November 1 Journal of the American Medical
Association and was conducted by researchers in the laboratory of Hannah
Kinney, M.D., at Children's Hospital Boston and Harvard Medical School as
well as other institutions.
"This finding lends credence to the view that SIDS risk may greatly increase
when an underlying predisposition combines with an environmental risk — such
as sleeping face down — at a developmentally sensitive time in early life,"
said Duane Alexander, M.D., Director of the NIH's National Institute of
Child Health and Human Development.
SIDS is the sudden and unexpected death of an infant under 1 year of age,
which cannot be explained after a complete autopsy, an investigation of the
scene and circumstances of the death, and a review of the medical history of
the infant and his or her family. Typically, the infant is found dead after
having been put to sleep and shows no signs of having suffered. In previous
studies, researchers have hypothesized that abnormalities in the brainstem
may make an infant susceptible to situations in which they re-breathe their
own exhaled breath, depriving them of oxygen. This hypothesis holds that
certain infants may not be able to detect high carbon dioxide or low oxygen
levels during sleep, and do not wake up.
To conduct the current study, researchers examined tissue from the
brainstems of 31 infants who died of SIDS and 10 infants who died of other
causes. The tissue was provided by the office of the chief medical examiner
in San Diego, California, and was collected from infants who died between
1997 and 2005.
The lower brainstem helps control such basic functions as breathing, heart
rate, blood pressure, body temperature, and arousal. The researchers found
that brainstems from SIDS infants contained more neurons (brain or nerve
cells) that manufacture and use serotonin than did the brainstems of the
control infants, explained the study's first author, David Paterson, PhD, a
researcher at Children's Hospital in Boston.
Serotonin belongs to a class of molecules known as neurotransmitters, which
serve to relay messages between neurons. Neurons release neurotransmitters,
which fit into special sites, or receptors, on surrounding neurons, somewhat
like a key fits into a lock. Once in place, the neurotransmitter either
promotes or hinders electrical activity in the receiving neuron — next in
line in a particular brain circuit — causing it to release its
neurotransmitters, which either excite or inhibit still more neurons, and so
on.
Although the brainstem tissue from the SIDS infants contained more
serotonin-using neurons, these serotonin-using neurons appeared to contain
fewer receptors for serotonin than did the brainstems of control infants.
Dr. Paterson noted that there are at least 14 different subtypes of
serotonin receptor. In their study, the researchers tested the infants'
brainstem tissue for a serotonin receptor known as "subtype 1A."
Tissue from both the SIDS infants and the control infants contained roughly
equal amounts of a key brain protein, serotonin transporter protein. This
protein recycles serotonin, collecting the neurotransmitter from the
surrounding spaces outside the neuron and transporting it back into
the neuron so it can be used again. Dr. Paterson explained, however, that
because the SIDS infants had proportionately more serotonin-using neurons
than did the control infants, they would also be expected to have more
serotonin transporter protein. So even though they had equal amounts of
serotonin transporter protein, the levels were nevertheless reduced —
relative to the increased number of serotonin-using neurons — and, for this
reason, unlikely to meet the needs of these cells.
Dr. Paterson added that from the observations in this study it was not
possible to determine how much serotonin the infants' brainstems contained
when the infants were alive. He noted, however, that the pattern of
abnormalities — more serotonin neurons, an apparent reduction of serotonin
1A receptors, and insufficient serotonin transporter — suggested that the
level of serotonin in the brainstems of SIDS infants was abnormal.
"Our hypothesis right now is that we're seeing a compensation mechanism,"
Dr. Paterson said. "If you have more serotonin neurons, it may be because
you have less serotonin and more neurons are recruited to produce and use
serotonin to correct this deficiency." The researchers also found that male
SIDS infants had fewer serotonin receptors than did either female SIDS
infants or control infants. The
finding may provide insight into why SIDS affects roughly twice as many
males as females.
"These findings provide evidence that SIDS is not a mystery but a disorder
that we can investigate with scientific methods, and some day, may be able
to identify and treat," said Dr. Hannah Kinney, the senior author of the
paper. A large body of research has shown that placing an infant to
sleep on his or her stomach greatly increases the risk of SIDS. The NICHD-sponsored
Back to Sleep campaign urges parents and caregivers to place infants to
sleep on their backs, to reduce SIDS risk. The campaign has reduced the
number of SIDS deaths by about half since it began in 1994. The campaign
also cautions against other practices that increase the risk of SIDS, such
as soft bedding, smoking during pregnancy, and smoking around a baby after
birth.
Despite the fact that the Back to Sleep Campaign recommendations had been
widely distributed by the time the study began, a large proportion of the
SIDS cases in the study by Drs. Paterson, Kinney and their coworkers were
correlated with known SIDS risk factors: 15 (48 percent) were found sleeping
on their stomachs, 9 (29 percent) were found face down, and 7 (23 percent)
were sharing a bed, at the time of death. "The majority (65 percent) of the
SIDS cases in this data set, however, were sleeping prone or on their side
at the time of death, indicating the need for continued public health
messages on safe sleeping practices, the study authors wrote."
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