Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration

Liya Qin, Xuefei Wu, Michelle Block, Yuxin Liu, George R. Breese, Jau Shyong Hong, Darin J. Knapp, Fulton T. Crews

Research output: Contribution to journalArticle

1128 Citations (Scopus)

Abstract

Inflammation is implicated in the progressive nature of neurodegenerative diseases, such as Parkinson's disease, but the mechanisms are poorly understood. A single systemic lipopolysaccharide (LPS, 5 mg/kg, i.p.) or tumor necrosis factor alpha (TNFα, 0.25 mg/kg, i.p.) injection was administered in adult wild-type mice and in mice lacking TNFα receptors (TNF R1/R2 -/-) to discern the mechanisms of inflammation transfer from the periphery to the brain and the neurodegenerative consequences. Systemic LPS administration resulted in rapid brain TNFα increase that remained elevated for 10 months, while peripheral TNFα (serum and liver) had subsided by 9 h (serum) and 1 week (liver). Systemic TNFα and LPS administration activated microglia and increased expression of brain pro-inflammatory factors (i.e., TNFα, MCP-1, IL-1β, and NF-κB p65) in wild-type mice, but not in TNF R1/R2-/- mice. Further, LPS reduced the number of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra (SN) by 23% at 7-months post-treatment, which progressed to 47% at 10 months. Together, these data demonstrate that through TNFα, peripheral inflammation in adult animals can: (1) activate brain microglia to produce chronically elevated proinflammatory factors; (2) induce delayed and progressive loss of DA neurons in the SN. These findings provide valuable insight into the potential pathogenesis and self-propelling nature of Parkinson's disease.

Original languageEnglish (US)
Pages (from-to)453-462
Number of pages10
JournalGLIA
Volume55
Issue number5
DOIs
StatePublished - Apr 1 2007
Externally publishedYes

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Receptors, Tumor Necrosis Factor, Type II
Brain
Microglia
Substantia Nigra
Inflammation
Parkinson Disease
Neurons
Tumor Necrosis Factor Receptors
Liver
Tyrosine 3-Monooxygenase
Serum
Interleukin-1
Neurodegenerative Diseases
Lipopolysaccharides
Tumor Necrosis Factor-alpha
Injections
Therapeutics

Keywords

  • LPS
  • Microglia
  • Neurodegeneration
  • Neuroinflammation
  • Substantia nigra
  • TNFα

ASJC Scopus subject areas

  • Immunology

Cite this

Qin, L., Wu, X., Block, M., Liu, Y., Breese, G. R., Hong, J. S., ... Crews, F. T. (2007). Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. GLIA, 55(5), 453-462. https://doi.org/10.1002/glia.20467

Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. / Qin, Liya; Wu, Xuefei; Block, Michelle; Liu, Yuxin; Breese, George R.; Hong, Jau Shyong; Knapp, Darin J.; Crews, Fulton T.

In: GLIA, Vol. 55, No. 5, 01.04.2007, p. 453-462.

Research output: Contribution to journalArticle

Qin, L, Wu, X, Block, M, Liu, Y, Breese, GR, Hong, JS, Knapp, DJ & Crews, FT 2007, 'Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration', GLIA, vol. 55, no. 5, pp. 453-462. https://doi.org/10.1002/glia.20467
Qin, Liya ; Wu, Xuefei ; Block, Michelle ; Liu, Yuxin ; Breese, George R. ; Hong, Jau Shyong ; Knapp, Darin J. ; Crews, Fulton T. / Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration. In: GLIA. 2007 ; Vol. 55, No. 5. pp. 453-462.
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