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  Previous issue (2022. Vol. 20, no. 1)

Autism and Developmental Disorders

Publisher: Moscow State University of Psychology and Education

ISSN (printed version): 1994-1617

ISSN (online): 2413-4317


License: CC BY-NC 4.0

Published since 2003

Published quarterly

Free of fees
Open Access Journal


GABA and Glutamate Imbalance in Autism and Their Reversal as Novel Hypothesis for Effective Treatment Strategy 1248


El-Ansary A.
PhD, professor of the Central laboratory, Female Centre for Scientific and Medical Studies, King Saud University, Riyadh, Saudi Arabia

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by reduced social communication and repetitive behaviors. The etiological mechanisms of ASD are still unknown; however, the GABAergic system has received considerable attention due to its potential as a therapeutic target. Based on the fact that individuals with autism demonstrate altered gene expression concomitant with impaired blood brain barrier (BBB), and gut barrier integrities, so increased glutamate levels in the blood and platelets of ASD patients can be related to lower numbers of cerebellar GABAergic neurons, less active GABA-synthesizing enzymes, and decreased brain GABA levels. Excitotoxic levels of released glutamate trigger a cascade of deleterious cellular events leading to delayed neuronal death. According to our understanding of glutamate excitotoxicity, GABA supplementation could theoretically be useful to treat certain autistic phenotypes. While there is still no effective and safe medication for glutamate-related cell damage and death, combined efforts will hopefully develop better treatment options. Here I hypothesize that an integrated treatment strategy with GABA supplements, regulation of chloride (Cl-) and magnesium (Mg2+) levels, vitamin D supplements, probiotics to enhance GABAA receptor and glutamate decarboxylase (GAD) expression, and memantine to activate glutamate transporters and inhibit NMDA receptors, could collectively reduce glutamate levels, maintain functional GABA receptors and thus treat repetitive behavior, impaired social behavior, and seizure activity in individuals with autism.

Keywords: autism; glutamate excitotoxicity; gamma-aminobutyric acid; vitamin D; gut microbiota

Column: Research & Diagnosis of ASD


Funding. This project was funded by the National Plan for Science Technology and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Kingdom of Saudi Arabia, Award number: 08-MED 510-02

Acknowledgements. The author thank the Deanship of Scientific Research and RSSU at King Saud University for their technical support.” Special thanks for Mrs Ramesa Shafi Bhat, Biochemistry Department, College of Science, KSU for her great efforts in improving the manuscript

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