Abstract
Autism is a debilitating neurodevelopment disorder characterised by stereotyped interests and behaviours, and abnormalities in verbal and non-verbal communication. It is 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. Substantial evidence suggests that excitotoxicity, oxidative stress and impaired mitochondrial function are the leading cause of neuronal dysfunction in autistic patients. Glutamate is the primary excitatory neurotransmitter produced in the CNS, and overactivity of glutamate and its receptors leads to excitotoxicity. The over excitatory action of glutamate, and the glutamatergic receptors NMDA and AMPA, leads to activation of enzymes that damage cellular structure, membrane permeability and electrochemical gradients. The role of excitotoxicity and the mechanism behind its action in autistic subjects is delineated in this review.
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Acknowledgments
The project was supported by Sultan Qaboos University; Oman in the form of internal grant is gratefully acknowledged (IG/AGR/FOOD/11/02) and also partly supported by the Research Council; Oman (Grant # RC/AGR/FOOD/11/01) as Post-Doctoral fellowship to Dr. Subash S. The scholarship given by Sultan Qaboos University to Vijayan KR is gratefully acknowledged. This work has been also supported by the National Health and Medical Research Council (NHMRC) and by the Rebecca Cooper foundation (Australia). Dr. Nady Braidy is the recipient of an Alzheimer’s Australia Viertel Foundation Postdoctoral Research Fellowship at the University of New South Wales.
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Essa, M.M., Braidy, N., Vijayan, K.R. et al. Excitotoxicity in the Pathogenesis of Autism. Neurotox Res 23, 393–400 (2013). https://doi.org/10.1007/s12640-012-9354-3
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DOI: https://doi.org/10.1007/s12640-012-9354-3