4.2 Article

GABA synaptopathy promotes the elevation of caspases 3 and 9 as pro-apoptotic markers in Egyptian patients with autism spectrum disorder

Journal

ACTA NEUROLOGICA BELGICA
Volume 121, Issue 2, Pages 489-501

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s13760-019-01226-z

Keywords

Autism; Caspases; GABA; Glutamate excitotoxicity; Synapses

Funding

  1. Research Center of the Center for Female Scientific and Medical Colleges at King Saud University

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Autism spectrum disorder (ASD) is characterized by reduced social communication and repetitive behaviors. Studies have shown that GABA levels are reduced in ASD patients, while levels of caspases 3 and 9 are elevated. Analysis of data and curves suggest that these biomarkers may be utilized for the diagnosis of autism.
Autism spectrum disorder (ASD) is classified as a neurodevelopmental disorder characterized by reduced social communication as well as repetitive behaviors. Many studies have proved that defective synapses in ASD influence how neurons in the brain connect and communicate with each other. Synaptopathies arise from alterations that affecting the integrity and/or functionality of synapses and can contribute to synaptic pathologies. This study investigated the GABA levels in plasma being an inhibitory neurotransmitter, caspase 3 and 9 as pro-apoptotic proteins in 20 ASD children and 20 neurotypical controls using the ELISA technique. Analysis of receiver-operating characteristic (ROC) of the data that was obtained to evaluate the diagnostic value of the aforementioned evaluated biomarkers. Pearson's correlations and multiple regressions between the measured variables were also done. While GABA level was reduced in ASD patients, levels of caspases 3 and 9 were significantly higher when compared to neurotypical control participants. ROC and predictiveness curves showed that caspases 3, caspases 9, and GABA might be utilized as predictive markers in autism diagnosis. The present study indicates that the presence of GABAergic dysfunction promotes apoptosis in Egyptian ASD children. The obtained GABA synaptopathies and their connection with apoptosis can both relate to neuronal excitation, and imbalance of the inhibition system, which can be used as reliable predictive biomarkers for ASD.

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