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 overactivation of glutamate receptors triggers excitotoxicity. Hyperactivation of glutamatergic receptors, NMDA and 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.