Vol.:(0123456789) 1 3 Acta Neurologica Belgica https://doi.org/10.1007/s13760-019-01226-z ORIGINAL ARTICLE GABA synaptopathy promotes the elevation of caspases 3 and 9 as pro‑apoptotic markers in Egyptian patients with autism spectrum disorder Afaf El‑Ansary 1,2,3,4,5  · Naima Zayed 2  · Laila Al‑Ayadhi 4,5  · Hanan Qasem 5  · Mona Anwar 6  · Nagwa A. Meguid 6,7  · Ramesa Shaf Bhat 8  · Monica Daniela Doşa 9  · Salvatore Chirumbolo 10,11  · Geir Bjørklund 12 Received: 9 July 2019 / Accepted: 10 October 2019 © Belgian Neurological Society 2019 Abstract Autism spectrum disorder (ASD) is classifed as a neurodevelopmental disorder characterized by reduced social communi- cation as well as repetitive behaviors. Many studies have proved that defective synapses in ASD infuence how neurons in the brain connect and communicate with each other. Synaptopathies arise from alterations that afecting 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 signifcantly 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 synap- topathies 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. Keywords Autism · Caspases · GABA · Glutamate excitotoxicity · Synapses * Monica Daniela Doşa monicadanielad@yahoo.com * Geir Bjørklund bjorklund@conem.org 1 Central Laboratory, Female Centre for Scientifc and Medical Studies, King Saud University, Riyadh, Saudi Arabia 2 Therapeutic Chemistry Department, National Research Centre, Dokki, Cairo, Egypt 3 CONEM Saudi Autism Research Group, King Saud University, Riyadh, Saudi Arabia 4 Department of Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia 5 Autism Research and Treatment Center, Riyadh, Saudi Arabia 6 Department of Research on Children with Special Needs, National Research Centre, Giza, Egypt 7 CONEM Egypt Child Brain Research Group, National Research Center, Giza, Egypt 8 Biochemistry Department, College of Sciences, King Saud University, Riyadh, Saudi Arabia 9 Department of Pharmacology, Faculty of Medicine, Ovidius University, Constanța, Romania 10 Department of Neuroscience, Biomedicine and Movement Sciences, University of Verona, Verona, Italy 11 CONEM Scientifc Secretary, Verona, Italy 12 Council for Nutritional and Environmental Medicine (CONEM), Toften 24, 8610 Mo i Rana, Norway