Lipopolysaccharide mitagates methamphetamine-induced striatal dopamine depletion via modulating local TNF-α and dopamine transporter expression
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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In rhesus monkeys, chronic methamphetamine increases striatal expression of TNF and NF-κB.
“and striatal expression of TNF and NF-κB (Lai et al., 2009)”
From Stress- and Glucocorticoid-Induced Priming of Neuroinflammatory Responses: Potential Mechanisms of Stress-Induced Vulnerability to Drugs of Abuse (2011) · cites this paper as Lai et al., 2009
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“In rhesus monkeys, chronic Meth increased interferon a/b in frontal lobe (Coutinho et al., 2008) and striatal expression of TNF and NF-jB (Lai et al., 2009).”
BackgroundBuchanan, J. B., Sparkman, N. L., & Johnson, R. W. (2010) · Journal of Neuroinflammation · doi:10.1186/1742-2094-7-82 · Cited by 35 · see citing works
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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