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

: 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 hippocampus.