Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

被引：34

作者：

Hozumi, Hiroaki ^{[2
]}

Asanuma, Masato ^{[1
]}

Miyazaki, Ikuko ^{[1
]}

Fukuoka, Saki ^{[2
]}

Kikkawa, Yuri ^{[1
]}

Kimoto, Naotaka ^{[1
]}

Kitamura, Yoshihisa ^{[3
]}

Sendo, Toshiaki ^{[2
]}

Kita, Taizo ^{[4
]}

Gomita, Yutaka ^{[2
,5
]}

机构：

[1] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Brain Sci, Okayama 7008558, Japan

[2] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Clin Pharmacol & Pharm, Okayama 7008558, Japan

[3] Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Pharmaceut Care & Hlth Sci, Okayama 7008558, Japan

[4] Kyushu Nutr Welf Univ, Grad Sch Food & Nutr, Pharmacol Lab, Kitakyushu, Fukuoka 8038511, Japan

[5] Shujitsu Univ, Sch Pharm, Okayama 7038516, Japan

来源：

TOXICOLOGY LETTERS | 2008年 / 177卷 / 02期

关键词：

dopamine transporter; hyperthermia; interferon-gamma; methamphetamine; neuroprotection; neurotoxicity;

D O I：

10.1016/j.toxlet.2008.01.005

中图分类号：

R99 [毒物学（毒理学）];

学科分类号：

100405 [卫生毒理学];

摘要：

Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-gamma (IFN-gamma) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-gamma before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-gamma before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-gamma injection had no effect on METH-induced hyperthermia. In addition, IFN-gamma injected centrally after METH treatment, but not systemically, 1 h after the final METH injection significantly protected against METH-induced neurotoxicity. Our results suggest that IFN-gamma injected systemically or its related molecule protects against METH-induced neurotoxicity through intracerebral molecular pathways, while it can prevent METH-induced hyperthermia through different molecular events. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

引用

页码：123 / 129

页数：7

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