Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex

  • Ali Zare 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Alireza Ghanbari 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Mohammad Javad Hoseinpour 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
  • Mahdi Eskandarian Boroujeni 2. Department of Stem Cells and Regenerative Medicine, Faculty of Medical Biotechnology, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
  • Alimohammad Alimohammadi 3. Iranian Legal Medicine Organization, Tehran, Iran
  • Mohammad Amin Abdollahifar 4. Biology and Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Abbas Aliaghaei 4. Biology and Anatomical Sciences Department, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Vahid Mansouri 5. Faculty of Paramedical Science, Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  • Hamid Zaferani Arani 1. Young Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
Keywords: Methamphetamine; Prefrontal Cortex; Apoptosis; BDNF


Background: Methamphetamine (MA), is an extremely addictive stimulant that adversely affects the central nervous system. Accumulating evidence indicates that molecular mechanisms such as oxidative stress, apoptosis, and autophagy are involved in the toxicity of MA. Considering experimental animal studies exhibiting MA-induced neurotoxicity, the relevance of these findings needs to be evidently elucidated in human MA users. It is generally assumed that multiple chemical substances released in the brain following MA-induced metabolic activation are primary factors underlying damage of neural cells. Hence, this study aimed to investigate the role of autophagy and apoptosis as well as oxidative stress in the brain of postmortem MA-induced toxicity. Materials and Methods: In this study, we determine the gene expression of autophagy and apoptosis, including BECN1, MAP1ALC3, CASP8, TP53, and BAX genes in ten healthy controls and ten chronic users of MA postmortem dorsolateral prefrontal cortex (DLPFC) by real-time polymerase chain reaction. Also, we applied immunohistochemistry in formalin-fixed and paraffin-embedded human brain samples to analyze brain-derived neurotrophic factor (BDNF). Also, spectrophotometry was performed to measure glutathione (GSH) content. Results: The expression level of apoptotic and autophagic genes (BECN1, MAP1ALC3, CASP8, TP53, and BAX) were significantly elevated, while GSH content and BDNF showed substantial reductions in DLPFC of chronic MA users. Conclusion: Our data showed that MA addiction provokes transduction pathways, namely apoptosis and autophagy, along with oxidative mechanisms in DLPFC. Also, MA induces multiple functional and structural perturbations in the brain, determining its toxicity and possibly contributing to neurotoxicity. [GMJ.2021;10:e2016]


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How to Cite
Zare, A., Ghanbari, A., Hoseinpour, M. J., Eskandarian Boroujeni, M., Alimohammadi, A., Abdollahifar, M. A., Aliaghaei, A., Mansouri, V., & Zaferani Arani, H. (2021). Methamphetamine-Triggered Neurotoxicity in Human Dorsolateral Prefrontal Cortex. Galen Medical Journal, 10, e2016.
Original Article