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

Document Type : Research article


1 Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Proteomics Research Center, Faculty of Paramedicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

5 Cellular and Molecular Research Center, Faculty of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran.


Methamphetamine (Meth) is recognized as one of the most important new distributed
abused drug that causes severe damage to the different parts of the brain, especially
hippocampus. Previous studies have demonstrated that Meth can induce apoptosis and cell
death in the brain. In this study, we evaluated the long-term effects of Meth abuse in the
CA1 region of postmortem hippocampus. Postmortem molecular and histological analysis
was 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 western
blotting and immunohistochemistry (IHC) methods. Histopathological assessment was done
with 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-protein
interaction analysis network was investigated. Western blotting and immunohistochemistry
assay showed overexpression of GFAP and Iba-1 protein in the CA1 hippocampal region
of Meth users’ brain. Stereological analysis in the CA1 region revealed increased neuron
degeneration. Furthermore, significant apoptosis and cell death were confirmed by Tunel assay
in the hippocampus. The prominent role of TLR4, IL1B, CASP1, and NLRP3 in the molecular
mechanism of Meth was highlighted via PPI network analysis. Chronic Meth use can induce
GFAP and Iba-1 upregulation and neuronal apoptosis in the CA1 region of the postmortem


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