Disorder in glutamate regulation and microglial activity The incidence of autism spectrum disorders (ASD) has increased to the alarming rate of approximately 1 in 100, and in some areas of the country, as many as 1 in 67 males are afflicted with the condition.

ASD is a related group of neurodevelopmental disorders including autism, Asperger’s syndrome, Rett’s syndrome, childhood disintegrative syndrome, and pervasive developmental disorder not otherwise specified (PDD-NOS).

Until now, researchers have not proposed a theory that pinpoints a single mechanism responsible for causing the diverse constellation of behaviors characteristic of ASD. A research study published in Current Medicinal Chemistry proposes that environmental and dietary factors may trigger a devastating cycle of events affecting certain activities of the brain.

In their recent paper, researchers R.L. Blaylock and A. Strunecka propose that increased levels of glutamate, a neurotransmitter involved in more than half of the brain’s neural transmissions, is implicated in ASD.

Glutamate is essential for learning, memory, motor coordination, and many other brain functions. However, too much glutamate in the brain has toxic effects. The level of glutamate is regulated by a sophisticated feedback system. If this complex feedback system becomes impaired, a condition called excitotoxicity occurs which can trigger abnormal development of the nervous system. Studies have indicated that there is a genetic abnormality in the regulation of glutamate in individuals with ASD.

Also a part of the picture is an inflammatory process in the central nervous system (CNS). Immune cells in the CNS, called microglia, remove damaged nerve cells from the brain and CNS. However, when microglia are chronically active, they release damaging chemicals.

Chronic activity of the microglial cells leads to CNS damage and has been implicated in a number of neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. In 2005, brain autopsies of individuals with ASD confirmed the presence of significantly increased levels of microglial cell activation.

Blaylock and Strunecka comment, “As a multifaceted disorder, ASD requires a multifaceted approach, one that should include the protection against excitotoxicity/microglial activation.”

They warn of the significant dangers of long-term fluoride use, ingestion of aluminum, and diets containing processed foods, and aspartate-containing additives. They recommend “nutrition with special nutrients that have been shown to reduce excitotoxicity and microglial activation.”

They encourage the use of these compounds and supplements to reduce excitotoxicity:

  • Methylcobalamin (vitamin B12)
  • Pyridoxal-5 phosphate (vitamin B6)
  • Vitamin E (mixed tocopherols)
  • Vitamin C (buffered)
  • CoQ10
  • Acetyl-L-carnitine
  • Alpha-lipoic acid
  • Magnesium glycinate or lactate
  • Zinc
  • Flavonoids

They suggest the use of these supplements and compounds which reduce microglial activation:

  • Ibupropen
  • Mincycline
  • Ferulic acid
  • DHEA
  • Curcumin
  • Quercetin
  • Silymarin
  • Baicalein
  • Resveratrol
  • DHA/EPA

Their scholarly paper can be accessed here.

Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders
R.L. Blaylock and A. Strunecka
Current Medicinal Chemistry, 2009, Vol. 16

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