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.“