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

22 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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Hozumi, H., Asanuma, M., Miyazaki, I., Fukuoka, S., Kikkawa, Y., Kimoto, N., Kitamura, Y., Sendo, T., Kita, T., & Gomita, Y. (2008). Protective effects of interferon-γ against methamphetamine-induced neurotoxicity. Toxicology Letters, 177(2), 123-129. https://doi.org/10.1016/j.toxlet.2008.01.005

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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",

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AU - Hozumi, Hiroaki

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AU - Kikkawa, Yuri

AU - Kimoto, Naotaka

AU - Kitamura, Yoshihisa

AU - Sendo, Toshiaki

AU - Kita, Taizo

AU - Gomita, Yutaka

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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.

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KW - Neuroprotection

KW - Neurotoxicity

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