Excitotoxicity in the Pathogenesis of Autism

Autism is a neurodevelopmental disorder characterized by stereotyped interests and behaviors, and abnormalities in verbal and nonverbal communication. Autism is reported as a multifactorial disorder resulting from interactions between genetic, environmental, and immunological factors. Excitotoxicity and oxidative stress are potential mechanisms, which are likely to serve as a converging point to these risk factors. Numerous studies suggest that excitotoxicity is a likely cause of neuronal dysfunction in autistic patients. Glutamate is the main excitatory neurotransmitter generated in the CNS, and over activation of glutamate receptors triggers excitotoxicity. Hyperactivation of glutamatergic receptors, N-methyl-daspartate (NMDA) and 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate (AMPA), leads to activation of enzymes, which damage cellular structure, membrane permeability, and electrochemical gradients. The role of excitotoxicity in autistic subjects is summarized in this chapter.