Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

Hiroaki Hozumi; Masato Asanuma; Ikuko Miyazaki; Saki Fukuoka; Yuri Kikkawa; Naotaka Kimoto; Yoshihisa Kitamura; Toshiaki Sendo; Taizo Kita; Yutaka Gomita

doi:10.1016/j.toxlet.2008.01.005

Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

Hiroaki Hozumi, Masato Asanuma, Ikuko Miyazaki, Saki Fukuoka, Yuri Kikkawa, Naotaka Kimoto, Yoshihisa Kitamura, Toshiaki Sendo, Taizo Kita, Yutaka Gomita

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-γ (IFN-γ) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-γ before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-γ before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-γ injection had no effect on METH-induced hyperthermia. In addition, IFN-γ 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-γ 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.

Original language	English
Pages (from-to)	123-129
Number of pages	7
Journal	Toxicology Letters
Volume	177
Issue number	2
DOIs	https://doi.org/10.1016/j.toxlet.2008.01.005
Publication status	Published - Mar 15 2008

Keywords

Dopamine transporter
Hyperthermia
Interferon-γ
Methamphetamine
Neuroprotection
Neurotoxicity

ASJC Scopus subject areas

Toxicology

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10.1016/j.toxlet.2008.01.005

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@article{08194787665e47e69c7fefc26d07ae9d,

title = "Protective effects of interferon-γ against methamphetamine-induced neurotoxicity",

abstract = "Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-γ (IFN-γ) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-γ before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-γ before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-γ injection had no effect on METH-induced hyperthermia. In addition, IFN-γ 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-γ 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.",

keywords = "Dopamine transporter, Hyperthermia, Interferon-γ, Methamphetamine, Neuroprotection, Neurotoxicity",

author = "Hiroaki Hozumi and Masato Asanuma and Ikuko Miyazaki and Saki Fukuoka and Yuri Kikkawa and Naotaka Kimoto and Yoshihisa Kitamura and Toshiaki Sendo and Taizo Kita and Yutaka Gomita",

note = "Funding Information: 1 This work was supported in part by the Medical Research Service of the Veterans Administration, and by grants from the Southern California Chapter of the Arthritis Foundation and the USPHS, National Institute of Arthritis and Metabolic Diseases (AM-02375), and National Cancer Institute (CA-09120). Dr. McCombs is an Arthritis Foundation Postdoctoral Fellow. {\textquoteright} Address reprint requests to Joseph P. Michalski, M.D., Medical Research-151, Veterans Administration Medical Center, 5901 E. Seventh Street, Long Beach, Calif. 90822.",

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doi = "10.1016/j.toxlet.2008.01.005",

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T1 - Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

AU - Hozumi, Hiroaki

AU - Asanuma, Masato

AU - Miyazaki, Ikuko

AU - Fukuoka, Saki

AU - Kikkawa, Yuri

AU - Kimoto, Naotaka

AU - Kitamura, Yoshihisa

AU - Sendo, Toshiaki

AU - Kita, Taizo

AU - Gomita, Yutaka

N1 - Funding Information: 1 This work was supported in part by the Medical Research Service of the Veterans Administration, and by grants from the Southern California Chapter of the Arthritis Foundation and the USPHS, National Institute of Arthritis and Metabolic Diseases (AM-02375), and National Cancer Institute (CA-09120). Dr. McCombs is an Arthritis Foundation Postdoctoral Fellow. ’ Address reprint requests to Joseph P. Michalski, M.D., Medical Research-151, Veterans Administration Medical Center, 5901 E. Seventh Street, Long Beach, Calif. 90822.

PY - 2008/3/15

Y1 - 2008/3/15

N2 - Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-γ (IFN-γ) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-γ before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-γ before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-γ injection had no effect on METH-induced hyperthermia. In addition, IFN-γ 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-γ 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.

AB - Repeated injections of methamphetamine (METH) cause degeneration of striatal dopaminergic nerve terminals. In the present study, we examined the effects of interferon-γ (IFN-γ) on METH-induced striatal neurotoxicity in mice. Intraperitoneal injection of IFN-γ before METH injection significantly prevented METH-induced reduction of striatal dopamine transporter (DAT)-positive signals and hyperthermia. Furthermore, intracerebroventricular injection of IFN-γ before METH treatment markedly prevented METH-induced reduction of DAT. Interestingly, central IFN-γ injection had no effect on METH-induced hyperthermia. In addition, IFN-γ 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-γ 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.

KW - Dopamine transporter

KW - Hyperthermia

KW - Interferon-γ

KW - Methamphetamine

KW - Neuroprotection

KW - Neurotoxicity

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SN - 0378-4274

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ER -

Protective effects of interferon-γ against methamphetamine-induced neurotoxicity

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