Effects of Molecular Hydrogen on Methamphetamine-Induced Neurotoxicity and Spatial Memory Impairment

Di Wen, Rongji Hui, Jian Wang, Xi Shen, Bing Xie, Miao Gong, Feng Yu, Bin Cong, Chunling Ma

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DOI: 10.3389/fphar.2019.00823 DOI is the universal ID for this study.

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Methamphetamine (METH) is a highly addictive stimulant, and METH exposure can induce irreversible neuronal damage and cause neuropsychiatric and cognitive disorders. The ever-increasing levels of METH abuse worldwide have necessitated the identification of effective intervention strategies to protect the brain against METH-induced neurotoxicity. The protective effects of molecular hydrogen on oxidative stress and related neurodegenerative diseases have been recently elucidated. Herein, we investigated whether treatment with molecular hydrogen ameliorated the METH-induced neurotoxicity and spatial learning and memory impairments. Male C57BL/6 mice received four intraperitoneal METH injections (10 mg/kg, 3-h interval), and stereotypic behaviors and hyperthermia were observed. After METH treatment and behavioral observation, the mice were returned to their home cages, where they received water or hydrogen-rich water (HRW) ad libitum for 7 days. We found that the molecular hydrogen delivered by ad libitum HRW consumption significantly inhibited the METH-induced spatial learning impairment and memory loss evidenced in the Barnes maze and Morris water maze tests. Furthermore, molecular hydrogen significantly restrained the neuronal damage in the hippocampus after high-dose METH exposure. Ad libitum HRW consumption also had an inhibitory effect on the METH-induced increase in the expression of Bax/Bcl-2, cleaved caspase-3, glucose-related protein 78 (GRP 78), CCAAT/enhancer-binding protein homologous protein (CHOP), and p-NF-kB p65 expression and elevation of interleukin (IL)-6 and tumor necrosis factor (TNF)-α levels in the hippocampus. These are the first findings to indicate that hydrogen might ameliorate METH-induced neurotoxicity and has a potential application in reducing the risk of neurodegeneration frequently observed in METH abusers.

Publish Year 2019
Country China
Rank Positive
Journal Frontiers in Pharmacology
Primary Topic Brain
Secondary Topic Addiction
Model Mouse
Tertiary Topic Drug Toxicity (Methamphetamine)
Vehicle Water (Dissolved)
pH Neutral
Application Ingestion