Immune-glutamatergic dysfunction as a central mechanism of the autism spectrum disorders

• Published in: Current medicinal chemistry Vol. 16; no. 2; p. 157
• Main Authors: Blaylock, R L, Strunecka, A
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2009
• Subjects: Autistic Disorder - etiology; Autistic Disorder - immunology; Autistic Disorder - prevention & control; Brain - physiology; Brain - physiopathology; Child; Child, Preschool; Environmental Pollutants - toxicity; Glutamic Acid - metabolism; Humans; Immune System Diseases - genetics; Immune System Diseases - immunology; Microglia - immunology; Microglia - metabolism; Synaptic Transmission
• ISSN: 0929-8673
• DOI: 10.2174/092986709787002745

Despite the great number of observations being made concerning cellular and the molecular dysfunctions associated with autism spectrum disorders (ASD), the basic central mechanism of these disorders has not been proposed in the major scientific literature. Our review brings evidence that most heterogeneous symptoms of ASD have a common set of events closely connected with dysregulation of glutamatergic neurotransmission in the brain with enhancement of excitatory receptor function by pro-inflammatory immune cytokines as the underlying mechanism. We suggest that environmental and dietary excitotoxins, mercury, fluoride, and aluminum can exacerbate the pathological and clinical problems by worsening excitotoxicity and by microglial priming. In addition, each has effects on cell signaling that can affect neurodevelopment and neuronal function. Our hypothesis opens the door to a number of new treatment modes, including the nutritional factors that naturally reduce excitotoxicity and brain inflammation.