Necroptosis contributes to methamphetamine-induced cytotoxicity in rat cortical neurons
| Autor: | Kun Xiong, Jufang Huang, Lingling Long, Huidan Liao, Jie Yan, Yanjun Ding |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Necrosis Indoles Necroptosis Biology Pharmacology Toxicology Methamphetamine Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Annexin medicine Animals Propidium iodide Cytotoxicity Neurons Cell Death Tumor Necrosis Factor-alpha Neurotoxicity Imidazoles General Medicine medicine.disease Rats Microscopy Electron 030104 developmental biology chemistry Immunology Tumor necrosis factor alpha Female medicine.symptom 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicology in vitro : an international journal published in association with BIBRA. 35 |
| ISSN: | 1879-3177 |
| Popis: | Necroptosis, a programmed necrosis, is involved in various types of neurodegenerative diseases. In this study, we investigated whether necroptosis contributed to neuronal damage in a methamphetamine injury model. Methods: Primary cultures of embryonic cortical neurons from Sprague-Dawley rats were subjected to different doses of methamphetamine with/without pre-treatment with a specific necroptosis inhibitor, Necrostatin-1. Necrosis was assessed by determining lactate dehydrogenase release and by Annexin V/propidium iodide double staining, while the neuronal ultra-structure was examined by electron microscopy. Tumor necrosis factor-α protein levels were determined by enzyme-linked immunosorbent assay. Results: At early stages (12 h) of post-treatment with methamphetamine, significant necrosis occurred and the viability of neurons decreased in a dose- and time-dependent manner in this model of acute neuronal injury. Pretreatment with Necrostatin-1 led to significant neuronal preservation compared with the methamphetamine-treated groups. Furthermore, tumor necrosis factor-α expression increased in a dose-dependent manner following methamphetamine exposure. Conclusion: Methamphetamine induced necrosis in rat cortical neurons in vitro, both time and dose dependently, and necroptosis may be an important newly identified mode of cortical neuronal death caused by single high-dose methamphetamine administration. |
| Databáze: | OpenAIRE |
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