Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity.
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, 1h 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.
Hozumi
Hiroaki
H
Department of Clinical Pharmacology and Pharmacy, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Asanuma
Masato
M
Miyazaki
Ikuko
I
Fukuoka
Saki
S
Kikkawa
Yuri
Y
Kimoto
Naotaka
N
Kitamura
Yoshihisa
Y
Sendo
Toshiaki
T
Kita
Taizo
T
Gomita
Yutaka
Y
D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D019610:Cytoprotection; D015259:Dopamine Agents / Q000633:toxicity*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control*; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects
D016207:Cytokines; D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008694:Methamphetamine; D007371:Interferon-gamma