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Immune-Glutamatergic Dysfunction as a Central Mechanism of the Autism Spectrum Disorders

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Abstract:

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.

Keywords: Autism spectrum disorders; cytokines; excitotoxicity; fluoride; glutamatergic neurotransmission; inflammation; mercury; microglia

Document Type: Research Article

DOI: http://dx.doi.org/10.2174/092986709787002745

Affiliations: Laboratory of Neuropharmacology, 1st Faculty of Medicine, Charles University in Prague, Albertov 4, 128 00 Prague 2, Czech Republic.

Publication date: January 1, 2009

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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