astrocytes - brain cells at the root of epilepsy?

[Bernard]

In the study, Nedergaard and colleagues showed that astrocytes actually generate seizure activity, and the team linked astrocytes to a brain chemical long known to be a key player in the development of epilepsy. They showed that glutamate, which hypes up neurons and can make them fire uncontrollably, is released by astrocytes and can trigger seizure-like activity in the brain.

Then the team tested medications currently used to treat the disease. Epilepsy describes a condition in the brain where neurons start firing wildly and uncontrollably, sometimes resulting in seizures, and most medications aim to reduce such firing. The team showed that agents like gabapentin and valproate reduced the type of chemical signaling that causes astrocytes to release glutamate.

According to Nedergaard, many scientists have thought that epilepsy occurs when neurons that normally inhibit or slow down other neurons lose their power, as if the brakes on a speeding car were faulty. Current medications are aimed at making those molecular “brakes” more powerful and reining signals back in. But such drugs have side effects like drowsiness. Her work opens up a new avenue to understand the disease.

“The potential role of astrocytes in the generation of epilepsy has been largely ignored,” says Michel Berg, M.D., medical director of the Strong Epilepsy Center. “Epilepsy involves a re-organization of the brain’s pathways, in a way that is not completely understood, that results in recurrent seizures. Currently we have drugs to treat seizures, but not to prevent the whole process. Perhaps someday there will be ways to intervene before the circuitry is re-written, to prevent epilepsy completely.”

Roots of Epilepsy May Lie in Oft-Ignored Brain Cells

[Birdbomb]

Hmmmm...reserch for the root CAUSE and treatment rather than just treating the symptoms!

What a novel idea!

[Tilei]

First, cell experiments in petri dishes found that following an increase of the element calcium in astrocytes, there is an increase of calcium in surrounding neurons. This implied some form of communication between the two cell types. Next, scientists found that indeed the calcium increase in astrocytes directly links to changes in neuron activity. In one study of rat cells, microelectrodes measured the electrical impulses that neurons use to signal to each other. In response to the calcium increase in astrocytes, the majority of neurons tested slowed down their signaling activity...

Another fascinating discussion regarding the astocytes. We had also mentioned the addition of calcium, recommended by my Dr. to my regimen.

http://apu.sfn.org/content/Publicati...strocytes.html

[Bernard]

Nice find Tilei! I think researchers are just beginning to scratch the surface on understanding astrocytes. It looks like a very promising field.

[Herb]

Both articles are of interest to me from several viewpoints. One is the inter-relationship between Epilepsy and Depression, the crossover use of anti-epileptic drug for depression and the very same brain bio-neurologist-chemistry research for both Epilepsy and Depression.

Although both your finds are interesting what dismays me is the fact that Tilei’s posting is from December 2000 and Bernard’s posting is recent and essentially Bernard’s article rehashes exactly what was said 5 years ago. It appears the research is very, very slowly progressing and added to the fact the key word or words when reading any articles or research papers must be noted such as “may, hopeful, it might be possible” etc.

Research is indicating that glutamate “may” also be implicated in depression and relate back to glial cells. Maybe one day in my life time I’ll read a definitive answer to some of these illnesses instead of theories and/or suppositions and in the meantime we do the best we can with what we have.

In any event, thanks for sharing.

Herb

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[Shelley]

http://www.pslgroup.com/dg/DD64E.htm
This was e-mailed to me from another group that I belong to.

[RobinN]

In the book I am reading:
Excitotoxins: The Taste That Kills
talks about this area of the brain as being an area not protected by the blood brain barrier. This area can become damaged by free glutamates.

Dr Blaylock explains,

"Astrocytes are not nerve cells, but play a vital roll in the metabolic support of neurons."
"...we still must understand how the system works in the whole living organism. For example, when neurons are exposed to glutamate without astrocytes (special glial cells) being present, they are found to be on hundred times more sensitive to the toxic effects of this compound. So in this instance an experiment conducted to test the sensitivity of neurons to glutamate using tissue cultures containing only neurons would give us a false picture of the sensitivity of these neurons to glutamate in a whole brain by a factor of one hundred. Yet, man is a very unique species. On some occasions humans react to certain drugs and chemicals as no other animal. This maybe the case with excitotoxins. We know, for example, that the rhesus monkey is more resistant to the toxic effects of excitotoxins than is either man or mouse. This is because of the poor absorption of glutamate in monkeys. And as we have seen, human concentrate glutamate in their glood following a dose of MSG in higher concentrations than any other species of animal and are more sensitive to the toxic effects of this glutamate than are experimental animals.
Thus far, over seventy types of excitotoxins have been discovered...."

" There seems to be some difference in the sensitivity of some animals to these excitotoxins, even within the same species. For example, some animals require several times the dose of glutamate to produce the same brain cell destruction as in another animal of the exact species, sex, and weight. But then, all living things differ in their sensitivity to toxins. This may be because some cells are naturally stronger than others, or they maybe have more efficient protective mechanisms, such as the glutamate and calcium channel pumps."

"Part of the explanation as to why everyone does not develop these diseases after chronic exposure to excitotoxins lies in the competence of the various protective mechanisms used to prevent glutamate accumulation around the neuron. Remember, there is a pumping system that shunts excess glutamate into the surrounding astrocytes. If this system is very efficient, it will take enormous amounts of glutamate to produce brain lesions. But, also remember , this system is extremely energy dependent. If, for some reason, the energy supply is reduced, the protective pump will fail and toxic amounts of glutamate will accumulate around the neurons."

[speber]

...another interesting thread I'm following now!

[RobinN]

what is interesting is that when the excitotoxins are at toxic levels in the body, there are no outward signs. For years a baby may have gotten these in baby foods, when the brain was at the most vulnerable and the parent may not even know it until years later. In later stages of development the damage may present itself as an endocrine disorder or even possibly a learning disorder, or emotion control disorder. Mothers don't know that the MSG laced foods that they eat can effect the baby still in the womb. Toddler foods and processed snacks contain these ingredients.

Subtances labeled as "spices", "natural flavoring" and "flavoring" may contain anywhere from 30% to 60% MSG.

I thought I was shopping "healthy", but after a walk through my cupboards I was shocked.

[RobinN]

Epilepsy and brain pathology linked together by the protein ADK

The brain of individuals who suffer from epilepsy is characterized by astrogliosis, a brain pathology evidenced by a complex series of changes in the morphology and function of brain cells known as astrocytes. Little is known about how astrogliosis relates to the dysfunction of brain cells known as neurons in individuals with epilepsy, but filling in the blanks in our knowledge could lead to new possibilities for therapeutic intervention. A study using mice by Detlev Boison and colleagues at Legacy Clinical Research, Portland, has now identified the protein ADK in astrocytes as a molecular link between astrogliosis and neuronal dysfunction in epilepsy.

The authors observed in a mouse model of epilepsy that ADK upregulation and spontaneous seizures occurred in the region of the brain affected by astrogliosis. In addition, overexpression of ADK in a specific region of the brain triggered seizures in the absence of astrogliosis. Conversely, mice engineered to express less ADK in specific regions of the brain were protected from chemical-induced epilepsy. Furthermore, as ADK-deficient ES cell–derived implants protected normal mice from chemical-induced astrogliosis, ADK upregulation, and seizures, it was suggested that ADK-based treatment strategies might provide a new approach for the treatment of individuals with epilepsy.

http://www.eurekalert.org/pub_releas...-eab122607.php