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

  • Afaf El-Ansary
  • Naima Zayed
  • Laila Al-Ayadhi
  • Hanan Qasem
  • Mona Anwar
  • Nagwa A. Meguid
  • Ramesa Shafi Bhat
  • Monica Daniela DoşaEmail author
  • Salvatore Chirumbolo
  • Geir BjørklundEmail author
Original article

Abstract

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.

Keywords

Autism Caspases GABA Glutamate excitotoxicity Synapses 

Notes

Acknowledgements

This research project was supported by a grant from the Research Center of the Center for Female Scientific and Medical Colleges at King Saud University.

Author contributions

All authors confirmed that they have contributed to the intellectual content of this paper and have met the following three requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.

Funding

Funding was provided by the Research Center of the Center for Female Scientific and Medical Colleges at King Saud University.

Compliance with ethical standards

Conflict of interest

The authors declare no potential conflicts of interest with respect to the authorship, and/or publication of this article.

Ethical approval

All procedures performed were in accordance with the ethical standards of the institutional and/or national research committee, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Copyright information

© Belgian Neurological Society 2019

Authors and Affiliations

  1. 1.Central Laboratory, Female Centre for Scientific and Medical StudiesKing Saud UniversityRiyadhSaudi Arabia
  2. 2.Therapeutic Chemistry DepartmentNational Research CentreCairoEgypt
  3. 3.CONEM Saudi Autism Research GroupKing Saud UniversityRiyadhSaudi Arabia
  4. 4.Department of Physiology, College of MedicineKing Saud UniversityRiyadhSaudi Arabia
  5. 5.Autism Research and Treatment CenterRiyadhSaudi Arabia
  6. 6.Department of Research on Children with Special NeedsNational Research CentreGizaEgypt
  7. 7.CONEM Egypt Child Brain Research GroupNational Research CenterGizaEgypt
  8. 8.Biochemistry Department, College of SciencesKing Saud UniversityRiyadhSaudi Arabia
  9. 9.Department of Pharmacology, Faculty of MedicineOvidius UniversityConstanțaRomania
  10. 10.Department of Neuroscience, Biomedicine and Movement SciencesUniversity of VeronaVeronaItaly
  11. 11.CONEM Scientific SecretaryVeronaItaly
  12. 12.Council for Nutritional and Environmental Medicine (CONEM)Mo i RanaNorway

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