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Excitotoxicity in the Pathogenesis of Autism

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Handbook of Neurotoxicity

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Abstract

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-d-aspartate (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.

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Abbreviations

AMPA:

2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionate

iNOS:

Inducible nitric oxide

MRI:

Magnetic resonance imaging

NMDA:

N-methyl-d-aspartate

NO•:

Nitric oxide

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Acknowledgments

The work has been partly supported by Sultan Qaboos University Internal grant (Grant # IG/AGR/FOOD/11/02) and the Research Council; Oman (Grant # RC/AGR/FOOD/11/01). This work has been also supported by the Alzheimer’s Association (grant # IIRG- 08-89545) 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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Authors and Affiliations

  1. Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Muscat, Oman

    M. M. Essa, S. Subash & R. K. Vijayan

  2. School of Medical Sciences, Department of Pharmacology, Faculty of Medicine, University of NSW, Sydney, NSW, Australia

    M. M. Essa & G. J. Guillemin

  3. Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia

    N. Braidy

  4. St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, NSW, Australia

    G. J. Guillemin

  5. Neuropharmacology Group, MND and Neurodegenerative Diseases Research Centre, Macquarie University, Macquarie Park, NSW, Australia

    G. J. Guillemin

Authors
  1. M. M. Essa
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  2. N. Braidy
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  3. S. Subash
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  4. R. K. Vijayan
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  5. G. J. Guillemin
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Corresponding author

Correspondence to N. Braidy .

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Editors and Affiliations

  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Essa, M.M., Braidy, N., Subash, S., Vijayan, R.K., Guillemin, G.J. (2022). Excitotoxicity in the Pathogenesis of Autism. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_148-1

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  • DOI: https://doi.org/10.1007/978-3-030-71519-9_148-1

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-71519-9

  • Online ISBN: 978-3-030-71519-9

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