Postmortem Study of Molecular and Histological Changes in the CA1 Hippocampal Region of Chronic Methamphetamine User

Authors

  • Gholam-Reza Mahmoudiasl Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Hojjat Allah Abbaszadeh Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Maryam Sadat Khoramgah Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Mohammad-Amin Abdollahifar Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Mostafa Rezaei-Tavirani Proteomics Research Center, Faculty of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Shahram Darabi Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.
  • Somayeh Niknazar Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
  • Yousef Sadeghi Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. | Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Abstract:

Methamphetamine (Meth) is recognized as one of the most important new distributedabused drug that causes severe damage to the different parts of the brain, especiallyhippocampus. Previous studies have demonstrated that Meth can induce apoptosis and celldeath in the brain. In this study, we evaluated the long-term effects of Meth abuse in theCA1 region of postmortem hippocampus. Postmortem molecular and histological analysiswas performed for five non-addicted subjects and five Meth addicted ones. Iba-1 (microglia)and glial fibrillary acidic protein, GFAP (astrocytes) expression were assayed by westernblotting and immunohistochemistry (IHC) methods. Histopathological assessment was donewith stereological counts of hippocampal cells stained with hematoxylin and eosin (H and E).Tunel staining was used to detect DNA damage in human brains. In addition, protein-proteininteraction analysis network was investigated. Western blotting and immunohistochemistryassay showed overexpression of GFAP and Iba-1 protein in the CA1 hippocampal regionof Meth users’ brain. Stereological analysis in the CA1 region revealed increased neurondegeneration. Furthermore, significant apoptosis and cell death were confirmed by Tunel assayin the hippocampus. The prominent role of TLR4, IL1B, CASP1, and NLRP3 in the molecularmechanism of Meth was highlighted via PPI network analysis. Chronic Meth use can induceGFAP and Iba-1 upregulation and neuronal apoptosis in the CA1 region of the postmortemhippocampus.

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Journal title

volume 18  issue 4

pages  2067- 2082

publication date 2019-12-01

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