#CMSC16 – High Glutamate Levels in Brain Seen to Drive MS Progression

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disease progression in MS

Patients with multiple sclerosis (MS) have increased levels of the neurotransmitter glutamate in their brains, lowering the levels of N-acetylaspartate (NAA) — a process that likely leads to the loss of brain volume. The findings indicate that glutamate might be a driver of neuronal cell death and disease progression in MS, and a potential target of new therapies.

The amino acid glutamate is the main nerve-signaling molecule, or neurotransmitter, responsible for excitatory signals in the brain. Despite its abundance, it is usually tightly controlled, as excessive are toxic to cells.

Numerous lines of evidence point to the possibility that glutamate toxicity might contribute to MS. In addition, studies have shown that MS patients have higher levels of the neurotransmitter in their cerebrospinal fluid during relapses.

Using an advanced magnetic resonance imaging (MRI) technique, researchers in previously found elevated glutamate levels in some types of MS brain lesions, as well as in normal-appearing white matter.

The Yale University scientists, in the study In vivo evidence of glutamate toxicity in multiple sclerosis, used MRI to measure glutamate in the brains of 343 individuals with MS, adding measures of NAA levels as well, and related the concentrations to each other and to the extent of change in brain volume over time, as the individuals were followed for an average of five years.

NAA is an amino acid, often used as a marker of brain health. Scientists believe it is involved in myelin maintenance in adults, but might also play a role in mitochondrial energy metabolism in neurons, and the control of water concentration inside cells.

Researchers reported in the Annals of Neurology journal that higher brain glutamate concentrations were linked to lower levels of NAA in both gray matter and in white matter without lesions. More importantly, the ratio of glutamate to NAA, but not the individual levels, could predict brain volume loss, with each 10 percent increase being associated with a 0.33 percent lower volume per year. The ratio could also be linked to some measures of clinical worsening, but not to walking ability and spinal cord injury.

Dr. Daniel Pelletier, a senior study author and a renowned MS expert from the Yale School of Medicine, will expand on the topic of glutamate and its role in MS at the upcoming Consortium of Multiple Sclerosis Centers (CMSC) 2016 Annual Meeting, being held June 1-4, in National Harbor, Maryland. Dr. Pelletier will give the Presidential Lecture, which he titled  “Genetic Variations Relating to Glutamate Concentration in the Brain.

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  1. Cynthia says:

    For the patient with not so much technical understanding what does this mean, in the means of life style: like eating habits or anything else?

  2. manfred pungartnik says:

    seems that Glutamate levels also play a role in ALS and subsequently Rilutek is prescribed for ALS…for what it may be worth , could Rilutek then also be beneficial for MS?????

  3. Shasha says:

    MSG may hurt people and is hidden in many foods with many different names on the labels instead of MSG name. Glutamine helps me…is not glutamate. It helps heal by gut lining and helps fuel the brain.

  4. A hypothesis about the positive effect LDN has on MS – it lowers glutamate in the brain. This was published 2005, sad the research has moved so slow on excess glutamate and MS.

    Med Hypotheses. 2005;64(4):721-4. Links
    Low dose naltrexone therapy in multiple sclerosis.Agrawal YP.
    Department of Pathology, The University of Iowa Roy J. and Lucille A. Carver College of Medicine, Room 153 B MRC, 200 Hawkins Drive, Iowa City, IA 52242-1182, USA. yashpal-agrawal@uiowa.edu
    The use of low doses of naltrexone for the treatment of multiple sclerosis (MS) enjoys a worldwide following amongst MS patients. There is overwhelming anecdotal evidence, that in low doses naltrexone not only prevents relapses in MS but also reduces the progression of the disease. It is proposed that naltrexone acts by reducing apoptosis of oligodendrocytes. It does this by reducing inducible nitric oxide synthase activity. This results in a decrease in the formation of peroxynitrites, which in turn prevent the inhibition of the glutamate transporters. Thus, the excitatory neurotoxicity of glutamate on neuronal cells and oligodendrocytes via activation of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid class of glutamate receptor is prevented. It is crucial that the medical community respond to patient needs and investigate this drug in a clinical trial. PMID: 15694688

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