Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration.
Accumulated evidence has indicated that neuroinflammation is one of the important etiologic factors of Parkinson's disease (PD). Earlier studies have employed the inflammogen lipopolysaccharide (LPS) to induce inflammation of dopaminergic neurons. Methamphetamine (MA) dopaminergic toxicity similar to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity is frequently cited as a model of PD. In the present study, we examined whether striatal LPS exposure potentiates MA-induced dopaminergic toxicity. Combined treatment with LPS and MA significantly potentiates behavioral impairment and dopaminergic deficit. However, this combination did not significantly alter the other monoaminergic systems (e.g., serotonin, norepinephrine, and histamine). Consistently, microglial activation, labeled by F4/80 or Iba-1 in the nigrostriatal region was more pronounced with the combined treatment of LPS and MA compared to either treatment alone, but this combination did not significantly alter the microglial activation in other brain regions (e.g., hippocampus, dorsal raphe nuclei, and locus ceruleus). Furthermore, neuroinflammation, oxidative stress, and pro-apoptotic changes in the striatum were more accentuated with combined treatment of LPS and MA compared to either treatment alone. In addition, it is important that cytoplasmic accumulation of alpha-synuclein was observed in the substantia nigra of mice treated with LPS plus MA, and that L-Dopa treatment significantly attenuated behavioral changes and dopaminergic deficits induced by LPS plus MA. These results suggest that combined treatment of LPS with MA is a potential animal model for PD.
School of Veterinary Medicine, Kangwon National University, Chunchon, South Korea.
Bae Dong
BD
Jung
Eun-Joo
EJ
Shin
Xuan-Khanh Thi
XK
Nguyen
Chun-Hui
CH
Jin
Jae-Hyung
JH
Bach
Seok Joo
SJ
Park
Seung-Yeol
SY
Nah
Myung-Bok
MB
Wie
Guoying
G
Bing
Hyoung-Chun
HC
Kim
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects*; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008694:Methamphetamine / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D010300:Parkinson Disease / Q000503:physiopathology
D000447:Aldehydes; D008070:Lipopolysaccharides; D008694:Methamphetamine; D008315:Malondialdehyde; C027576:4-hydroxy-2-nonenal