Do all of us at times need a brain cleaner? A recently developed method at the Weizmann Institute holds promise for treating brain injuries, according to the January 17, 2007 news release, "Brain cleaner." When glutamate is released by damaged or dying brain cells, the result is a flood that overexcites nearby cells and kills them. For the general consumer, such as a senior citizen looking for more information on the role glutamate plays in brain activity, you also may be interested in taking a look at the site, "The role of glutamate in dementia."
A new method for ridding the brain of excess glutamate has been developed at the Weizmann Institute of Science. This method takes a completely new approach to the problem, compared with previous attempts based on drugs that must enter the brain to prevent the deleterious action of glutamate.
Many drugs, however, can't cross the blood-brain barrier into the brain, while other promising treatments have proved ineffective in clinical trials. Prof. Vivian Teichberg, of the Institute's Neurobiology Department, working together with Prof. Yoram Shapira and Dr. Alexander Zlotnik of the Soroka Medical Center and Ben Gurion University of the Negev, has shown that in rats, an enzyme in the blood can be activated to "mop up" toxic glutamate spills in the brain and prevent much of the damage. This method may soon be entering clinical trials to see if it can do the same for humans.
Though the brain has its own means of recycling glutamate, injury causes the system to malfunction, leading to glutamate build up
Professor Teichberg reasoned that this problem could be circumvented by passing glutamate from the fluid surrounding brain cells into the bloodstream. But first, he had to have a clear understanding of the mechanism for moving glutamate from the brain to the blood. Glutamate concentrations are several times higher in the blood than in the brain, and the body must be able to pump the chemical 'upstream.' Glutamate pumps, called transporters, are found on the outsides of blood vessels, on cells that come into contact with the brain. These collect glutamate, creating small zones of high concentration from which the glutamate can then be released into the bloodstream.
Basic chemistry told him that he could affect the transporter activity by tweaking glutamate levels in the blood. When blood levels are low, the greater difference in concentrations causes the brain to release more glutamate into the bloodstream.
He uses an enzyme called GOT that is normally present in blood to bind glutamate chemically and inactivate it, effectively lowering levels in the blood and kicking transporter activity into high gear, according to the January 17, 2007 news release, "Brain cleaner." In their experiments, Teichberg and his colleagues used this method to scavenge blood glutamate in rats with simulated traumatic brain injury. They found that glutamate cleared out of the animals' brains effectively, and damage was prevented.
Yeda, the technology transfer arm of the Weizmann Institute, now holds a patent for this method, and a new company based on this patent, called "Braintact Ltd.," has been set up in Kiryat Shmona in northern Israel and is currently operating within the framework of Meytav Technological Incubator. The US FDA has assured the company of a fast track to approval. If all goes well, Phase I clinical trials are planned for the near future.
The method could potentially be used to treat such acute brain insults as head traumas and stroke, and prevent brain and nerve damage from bacterial meningitis or nerve gas. It may also have an impact on chronic diseases such as glaucoma, amyotrophic lateral sclerosis (ALS) or HIV dementia.
"Our method may work where others have failed, because rather than temporarily blocking the glutamate's toxic action with drugs inside the brain, it clears the chemical away from the brain into the blood, where it can't do harm anymore," Teichberg explained, according to the news release.
An injury to the brain can be devastating. When brain cells die, whether from head trauma, stroke or disease, a substance called glutamate floods the surrounding areas, overloading the cells in its path and setting off a chain reaction that damages whole swathes of tissue.
Glutamate is always present in the brain, where it carries nerve impulses across the gaps between cells
When this chemical is released by damaged or dying brain cells, the result is a flood that overexcites nearby cells and kills them. Professor Vivian I. Teichberg's research is supported by the M.D. Moross Institute for Cancer Research; the Nella and Leon Benoziyo Center for Neurosciences; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Mario Negri Institute for Pharmacological Research – Weizmann Institute of Science Exchange Program; the Ruth and Samuel Rosenwasser Charitable Fund; the estate of Dr. Frank Goldstein, Chevy Chase, MD; Mr. and Mrs. Irwin Green, Boca Raton, FL; and the estate of Anne Kinston, UK.
What is Glutamate?
Glutamate is an amino acid, found in all protein-containing foods. Amino acids are the building blocks of proteins. This amino acid is one of the most abundant and important components of proteins. Glutamate is found naturally in protein-containing foods such as cheese, milk, mushrooms, meat, fish, and many vegetables. Glutamate is also produced by the human body and is vital for metabolism and brain function. Tomato juice has a large amount of glutamate.
A lot of foods have naturally-occurring glutamate. But monosodium glutamate, MSG, when added to food as a flavor extender becomes a neurotoxin. Monosodium glutamate (MSG) has been shown to penetrate placental barrier and distribute almost evenly among embryonic tissues using 3H-Glu as a tracer, explains a study, "Transplacental neurotoxic effects of monosodium glutamate on specific brain areas of filial mice."
Monosodium glutamate, or MSG, is the sodium salt of glutamate. When MSG is added to foods, it provides a similar flavoring function as the glutamate that occurs naturally in food. MSG is comprised of nothing more than water, sodium and glutamate.
Glutamate is actually 10 times more abundant in human breast milk than in cow's milk. Glutamate-containing food ingredients, such as hydrolyzed protein and autolyzed yeast extract, also must be listed on food labels. When glutamate is a component of natural protein foods, like tomatoes, it is not listed separately on the label.
Too many cooks at home or in eateries may try to wake up tired food by adding MSG
Monosodium glutamate (MSG) is mistakenly used as a taste enhancer on usually overcooked or 'tired' foods that don't have left enough flavor because they've been stored a long time. Up to 40 percent of the USA population is allergic to MSG. See the articles, studies, and bibliography for reference on adverse reactions related to MSG in food at the Truth in Labeling site. Also see the article, "Monosodium Glutamate: Poison the Body to Better the Taste," at the World Wide Health Center Net site.
According to the Truth in Labeling site, "On March 13, 2009, President Obama stated, in part, that the nation’s decades-old food safety system is a 'hazard to public health.' While nominating Margaret Hamburg, M.D., the former New York Health Commissioner, for the position of FDA commissioner, he also indicated that he would be creating a Food Safety Working Group to coordinate food safety laws throughout government and to advise him on how to update them."
There are healthier, natural alternatives to MSG: Lemon, orange, cherry, or lime juice would be a better flavor enhancer
Even cooking with a small amount of organic wine (without added sulfites) is safer. MSG secretly addicts the consumer to the food by tricking the brain into thinking the food is more flavorful as it hits the taste buds on the tongue. The hidden goal is to make sure the consumer will return to the product or restaurant and order the same food again.
Instead of MSG, as a flavor enhancer, use natural, fresh food flavors, stock, or add a small amount of healthier spices, vegetables, or fruit juices without overpowering the aroma and flavor of the food. MSG is dangerous to the central nervous system. A long list of books have been written about its neurotoxicity. For your reference, a bibliography of 62 studies on the toxicity of MSG are listed at the bottom of the article, "This is What the Data Say About Monosodium Glutamate Toxicity and Human Adverse Reactions," compiled by Adrienne Samuels, Ph.D. May 2009.
You'll find MSG in salad dressings, a variety of restaurant foods, in several types of canned soups and vegetables, in various types of prepared fish or meat products, and in some bottled or canned savory sauces. Read the label before you buy the product because it's often hidden in foods you'd never think would contain MSG.
Why is MSG still listed at safe by the FDA? Will the Department of Agriculture and the FDA ever share information and connect, commit, and communicate better regarding what additives are being put in most foods? Related research is abundant.
When older adults have a vitamin D deficiency
Older individuals who are vitamin D deficient also tend to have compromised immune function, according to new research accepted for publication in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism. The study, "Vitamin D Deficiency is Associated with Inflammation in Older Irish Adults," is now published online, ahead of print in the The Endocrine Society's Journal of Clinical Endocrinology & Metabolism (JCEM).
Vitamin D deficiency may compromise immune function. Vitamin-deficient seniors are more likely to have biomarkers for heart disease and inflammation says a new study. Older individuals who are vitamin D deficient also tend to have compromised immune function, according to the new research.
Vitamin D plays an important role in helping the body absorb calcium needed for healthy bones
The skin naturally produces vitamin D when it is exposed to sunlight. People also obtain smaller amounts of the vitamin through foods, such as milk fortified with vitamin D. More than 1 billion people worldwide are estimated to have deficient levels of vitamin D due to limited sunshine exposure.
"Our data suggest vitamin D may be involved in maintaining the health of the immune system as well as the skeletal system," said one of the study's authors, Mary Ward, PhD, of the University of Ulster in Coleraine, U.K, according to the February 25, 2014 news release, Vitamin D deficiency may compromise immune function. "This study is the first to find a connection between vitamin D levels and inflammation in a large sample of older individuals." The observational study of 957 Irish adults who were at least 60 years old examined vitamin D levels as well as biomarkers of inflammation.
Participants who were vitamin D deficient were more likely to have high levels of these biomarkers, which are linked to cardiovascular disease and inflammatory conditions such as multiple sclerosis and rheumatoid arthritis
"The results indicate immune function may be compromised in older individuals with vitamin D deficiency," Ward said in the news release. "Ensuring older individuals have optimal vitamin D levels may be a way to boost immune function in this population, but this needs to be confirmed through additional studies."
Other authors of the study include: E. Laird and A.M. Molloy of Trinity College in Dublin, Ireland; H. McNulty, L. Hoey, E. McSorley, J.M.W. Wallace, E. Carson and J.J. Strain of the University of Ulster; and M. Healy, M. Casey and C. Cunningham of St. James's Hospital in Dublin.
Founded in 1916, the Endocrine Society is the world's oldest, largest and most active organization devoted to research on hormones and the clinical practice of endocrinology. Today, the Endocrine Society's membership consists of over 17,000 scientists, physicians, educators, nurses and students in more than 100 countries. Society members represent all basic, applied and clinical interests in endocrinology. The The Endocrine Society is based in Washington, DC. You also can follow the Endocrine Society on Twitter.
How increased brain cell activity boosts brain fluid levels of a protein linked to Alzheimer's disease
Increased brain cell activity boosts brain fluid levels of a protein linked to Alzheimer’s disease, according to new research in another study from scientists at Washington University School of Medicine in St. Louis. The study, "Neuronal activity regulates extracellular tau in vivo," is published online since February 18, 2014 in the Journal of Experimental Medicine. Tau protein is the main component of neurofibrillary tangles, one of the hallmarks of Alzheimer’s disease. It has been linked to other neurodegenerative disorders, including frontotemporal dementia, supranuclear palsy and corticobasal degeneration.
“Healthy brain cells normally release tau into the cerebrospinal fluid and the interstitial fluid that surrounds them, but this is the first time we’ve linked that release in living animals to brain cell activity,” said senior author David M. Holtzman, MD, according to the February 25, 2014 news release, Brain cell activity regulates Alzheimer’s protein . “Understanding this link should help advance our efforts to treat Alzheimer’s and other neurodegenerative disorders associated with the tau protein.
Tau protein stabilizes microtubules, which are long columns that transport supplies from the center of the cell to the distant ends of the cell’s branches
Some tau in the cell is not bound to microtubules. This tau can become altered and clump together inside brain cells, forming structures called tangles. Scientists have tracked the spread of these clumps through brain networks in animal models.
“In Alzheimer’s disease, you first see clumps of tau in a region called the entorhinal cortex, and then in the hippocampus, and it continues to spread through the brain in a regular pattern,” said Holtzman, the Andrew B. and Gretchen P. Jones Professor and head of the Department of Neurology, according to the news release. “In another disorder, supranuclear palsy, tau clumps first appear in the brain stem and then spread to regions that the brain stem projects to.”
These regular patterns of tau spread through brain networks have led scientists to speculate that dysfunctional tau travels to different brain regions via synapses — the areas where individual nerve cells communicate with each other.
Holtzman’s results support this hypothesis, showing that when nerve cells “talk” to each other, tau levels go up in the fluids between those cells, suggesting that brain cells are secreting tau when they send signals. So far, the researchers only have been able to measure single copies of tau in brain fluid, not the tau clumps. They are looking for a way to detect the clumps.
If brain cells can secrete and take in clumps of tau, the scientists believe, these clumps may cause previously normal tau in the receiving cell to become corrupted, fostering the spread of a form of tau involved in disease. “We also want to know whether brain cells are secreting tau as waste or if tau has a function to perform outside the cell,” Holtzman said in the news release. “For example, there have been hints that tau may modulate how easy or difficult it is to get brain cells to communicate with each other.”
The Tau Consortium and the Japan Society for the Promotion of Science supported the study. Authors are Yamada K, Holth JK, Liao F, Stewart FR, Mahan TE, Jiang H, Cirrito JR, Patel TK, Hochgräfe K, Mandelkow E-M, and David M. Holtzman. You can check out the abstract of the study online, "DM. Neuronal activity regulates extracellular tau in vivo," published online February. 18, 2014 in the Journal of Experimental Medicine.
Tau is primarily a cytoplasmic protein that stabilizes microtubules, according to the study's abstract
What happens is that tau also is found in the extracellular space of the brain at appreciable concentrations. Researchers are trying to understand more about tau. Although its presence there may be relevant to the intercellular spread of tau pathology, the cellular mechanisms regulating tau release into the extracellular space are not well understood. That's why the research focused on testing the context of neuronal networks.
To test this in the context of neuronal networks in vivo, the researchers used in vivo microdialysis. Increasing neuronal activity rapidly increased the steady-state levels of extracellular tau in vivo.
How does glutamate play a role?
Importantly, the researchers write in the study's abstract, presynaptic glutamate release is sufficient to drive tau release. Although tau release occurred within hours in response to neuronal activity, the elimination rate of tau from the extracellular compartment and the brain is slow (half-life of ~11 d). The in vivo results provide one mechanism underlying neuronal tau release and may link trans-synaptic spread of tau pathology with synaptic activity itself.
Glutamate is an excitatory neurotransmitter, but may also act as an endogenous neurotoxin, notes that study's abstract. There is good evidence for an involvement of the glutamatergic system in the pathophysiology of dementia.
The glutamatergic transmission machinery is quite complex and provides a gallery of possible drug targets. There are good arguments both for an agonist and an antagonist strategy. When following the antagonist strategy, the goal is to provide neuroprotective effects via glutamate receptor antagonisms without inhibiting the physiological transmission that is required for learning and memory formation.
The study's abstract explains that when following the agonist strategy, the goal is to activate glutamatergic transmission without neurotoxic side effects. Several available antidementia drugs may modulate the glutamatergic transmission. Fascinating topic how glutamate works in the brain. You may wish to check out the site, "Everything You Need To Know About Glutamate And Monosodium Glutamate."