Potentiation of methamphetamine neurotoxicity by intrastriatal lipopolysaccharide administration

Bae Dong Jung, Eun Joo Shin, Xuan Khanh Thi Nguyen, Chun Hui Jin, Jae Hyung Bach, Seok Joo Park, Seung Yeol Nah, Myung Bok Wie, Guoying Bing, Hyoung Chun Kim

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

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 α-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.

Original languageEnglish
Pages (from-to)229-244
Number of pages16
JournalNeurochemistry International
Volume56
Issue number2
DOIs
StatePublished - Jan 2010

Bibliographical note

Funding Information:
This study was supported by a grant ( #2009K001253 ) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea . Chun Hui Jin and Jae-Hyung Bach were supported by BK 21 program . Equipment at the Institute of Pharmaceutical Science (Kangwon National University) was used for this study.

Keywords

  • Apoptosis
  • Lipopolysaccharide
  • Methamphetamine
  • Neuroinflammation
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Cell Biology

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