Anatomy and Cell Biology

Korean Association of Anatomists (대한해부학회)
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Exploring amygdala structural changes and signaling pathways in postmortem brains: consequences of long-term methamphetamine addiction

  • Zahra Azimzadeh (Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences) ;
  • Samareh Omidvari (Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Somayeh Niknazar (Functional Neurosurgery Research Center, Shohada Tajrish Comprehensive Neurosurgical Center of Excellence, Shahid Beheshti University of Medical Sciences) ;
  • Saeed Vafaei-Nezhad (Department of Anatomical Sciences, School of Medicine, Cellular and Molecular Research Center, Birjand University of Medical Sciences) ;
  • Navid Ahmady Roozbahany (Private Practice) ;
  • Mohammad-Amin Abdollahifar (Department of Biology and Anatomical Sciences, School of Medicine, Shahid Beheshti University of Medical Sciences) ;
  • Foozhan Tahmasebinia (Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences) ;
  • Gholam-Reza Mahmoudiasl (Iranian Legal Medicine Organization) ;
  • Hojjat Allah Abbaszadeh (Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences) ;
  • Shahram Darabi (Cellular and Molecular Research Center, Research Institute for Non-Communicable Diseases, Qazvin University of Medical Sciences)
  • Received : 2023.07.16
  • Accepted : 2023.09.19
  • Published : 2024.03.31
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Abstract

Methamphetamine (METH) can potentially disrupt neurotransmitters activities in the central nervous system (CNS) and cause neurotoxicity through various pathways. These pathways include increased production of reactive nitrogen and oxygen species, hypothermia, and induction of mitochondrial apoptosis. In this study, we investigated the long-term effects of METH addiction on the structural changes in the amygdala of postmortem human brains and the involvement of the brain- cAMP response element-binding protein/brain-derived neurotrophic factor (CREB/BDNF) and Akt-1/GSK3 signaling pathways. We examined ten male postmortem brains, comparing control subjects with chronic METH users, using immunohistochemistry, real-time polymerase chain reaction (to measure levels of CREB, BDNF, Akt-1, GSK3, and tumor necrosis factor-α [TNF-α]), Tunnel assay, stereology, and assays for reactive oxygen species (ROS), glutathione disulfide (GSSG), and glutathione peroxidase (GPX). The findings revealed that METH significantly reduced the expression of BDNF, CREB, Akt-1, and GPX while increasing the levels of GSSG, ROS, RIPK3, GSK3, and TNF-α. Furthermore, METH-induced inflammation and neurodegeneration in the amygdala, with ROS production mediated by the CREB/BDNF and Akt-1/GSK3 signaling pathways.

Keywords

Acknowledgement

We extend our appreciation to the Iranian legal organization for their assistance.

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