Cited by 29Parkinson's Disease Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsTryptophan and brain disorders

Lipopolysaccharide mitagates methamphetamine-induced striatal dopamine depletion via modulating local TNF-α and dopamine transporter expression

Lai, Yu-Ting, Tsai, Yen-Ping N., Cherng, Chianfang G., Ke, Jing-Jer, Ho, Ming-Che, Tsai, Chia-Wen, Yu, Lung·2009·Journal of Neural Transmission

Abstract

Systemic lipopolysaccharide (LPS) treatment may affect methamphetamine (MA)-induced nigrostriatal dopamine (DA) depletion. This study was undertaken to determine the critical time window for the protective effects of LPS treatment and the underlying mechanisms. An LPS injection (1 mg/kg) 72 h before or 2 h after MA treatment [three consecutive, subcutaneous injections of MA (10 mg/kg each) at 2-h intervals] diminished the MA-induced DA depletion in mouse striatum. Such an LPS-associated effect was independent of MA-produced hyperthermia. TNF-alpha, IL-1beta, IL-6 expressions were all elevated in striatal tissues following a systemic injection with LPS, indicating that peripheral LPS treatment affected striatal pro-inflammatory cytokine expression. Striatal TNF-alpha expression was dramatically increased at 72 and 96 h after the MA treatment, while such TNF-alpha elevation was abolished by the LPS pretreatment protocol. Moreover, MA-produced activation of nuclear NFkappaB, a transcription factor following TNF-alpha activation, in striatum was abolished by the LPS (1 mg/kg) pretreatment. Furthermore, thalidomide, a TNF-alpha antagonist, treatment abolished the LPS pretreatment-associated protective effects. Pretreatment with mouse recombinant TNF-alpha in striatum diminished the MA-produced DA depletion. Finally, single LPS treatment caused a rapid down-regulation of dopamine transporter (DAT) in striatum. Taken together, we conclude that peripheral LPS treatment protects nigrostriatal DA neurons against MA-induced toxicity, in part, by reversing elevated TNF-alpha expression and subsequent signaling cascade and causing a rapid DAT down-regulation in striatum.

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Crossref · 10.1007/s00702-009-0204-2

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Authors
Lai, Y.-T., Tsai, Y.-P. N., Cherng, C. G., Ke, J.-J., Ho, M.-C., Tsai, C.-W., & Yu, L.
Affiliations
  • National Cheng Kung University (TW)
  • Chang Jung Christian University (TW)
Corresponding author
Yu, Lung
Venue
Journal of Neural Transmission
Published
2009-03-07
Volume
116
Issue
4
Pages
405-415
ISSN
  • 0300-9564 (ISSN-L)
  • 1435-1463
OpenAlex
W2047310207
Cited by
29
References
50
Citations by year
2026: 1 · 2025: 2 · 2022: 2 · 2021: 2 · 2020: 2 · 2019: 2 · 2016: 1 · 2015: 1 · 2014: 4 · 2013: 1 · 2012: 3
FWCI
2.34
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Neural Transmission (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
lipopolysaccharide, methamphetamine, dopamine depletion, striatum, nigrostriatal dopaminergic neurons, TNF-α, inflammatory cytokines, NF-κB, thalidomide, neuroprotection, neuroinflammation
MeSH terms
Animals, Corpus Striatum, Dopamine, Fever, Lipopolysaccharides, Male, Methamphetamine, Mice, Inbred C57BL, Thalidomide, Tumor Necrosis Factor-alpha, Interleukin-6, NF-kappa B, Dopamine Uptake Inhibitors, Dopamine Plasma Membrane Transport Proteins, Mice, Interleukin-1beta

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