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
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.
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.
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]
EMBARGOED FOR RELEASE
Tuesday, October 31, 2006
4:00 p.m. ET
or Marianne Glass Miller
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."