Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice

M. K. Larsson, A. Faka, M. Bhat, S. Imbeault, M. Goiny, F. Orhan, A. Oliveros, S. Ståhl, X. C. Liu, Doo Sup Choi, K. Sandberg, G. Engberg, L. Schwieler, S. Erhardt

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The immune system has been recognized as a potential contributor to psychiatric disorders. In animals, lipopolysaccharide (LPS) is used to induce inflammation and behaviors analogous to some of the symptoms in these disorders. Recent data indicate that the kynurenine pathway contributes to LPS-induced aberrant behaviors. However, data are inconclusive regarding optimal LPS dose and treatment strategy. Here, we therefore aimed to evaluate the effects of single versus repeated administration of LPS on the kynurenine pathway. Adult C57BL6 mice were given 0.83 mg/kg LPS as a single or a repeated injection (LPS + LPS) and sacrificed after 24, 48, 72, or 120 h. Mice receiving LPS + LPS had significantly elevated brain kynurenine levels at 24 and 48 h, and elevated serum kynurenine at 24, 48 and 72 h. Brain kynurenic acid and quinolinic acid were significantly increased at 24 and 48 h in mice receiving LPS + LPS, whereas serum kynurenic acid levels were significantly decreased at 24 h. The increase of brain kynurenic acid by LPS + LPS was likely unrelated to the higher total dose as a separate group of mice receiving 1.66 mg/kg LPS as single injection 24 h prior to sacrifice did not show increased brain kynurenic acid. Serum quinolinic acid levels were not affected by LPS + LPS compared to vehicle. Animals given repeated injections of LPS showed a more robust induction of the kynurenine pathway in contrast to animals receiving a single injection. These results may be valuable in light of data showing the importance of the kynurenine pathway in psychiatric disorders.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalNeurochemical Research
DOIs
StateAccepted/In press - May 10 2016

Fingerprint

Kynurenine
Lipopolysaccharides
Injections
Kynurenic Acid
Brain
Quinolinic Acid
Animals
Psychiatry
Serum
Immune system

Keywords

  • Kynurenic acid
  • Kynurenine pathway
  • Lipopolysaccharide
  • Neuroinflammation
  • Psychiatric disorders
  • Quinolinic acid

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

Larsson, M. K., Faka, A., Bhat, M., Imbeault, S., Goiny, M., Orhan, F., ... Erhardt, S. (Accepted/In press). Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice. Neurochemical Research, 1-13. https://doi.org/10.1007/s11064-016-1939-4

Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice. / Larsson, M. K.; Faka, A.; Bhat, M.; Imbeault, S.; Goiny, M.; Orhan, F.; Oliveros, A.; Ståhl, S.; Liu, X. C.; Choi, Doo Sup; Sandberg, K.; Engberg, G.; Schwieler, L.; Erhardt, S.

In: Neurochemical Research, 10.05.2016, p. 1-13.

Research output: Contribution to journalArticle

Larsson, MK, Faka, A, Bhat, M, Imbeault, S, Goiny, M, Orhan, F, Oliveros, A, Ståhl, S, Liu, XC, Choi, DS, Sandberg, K, Engberg, G, Schwieler, L & Erhardt, S 2016, 'Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice', Neurochemical Research, pp. 1-13. https://doi.org/10.1007/s11064-016-1939-4
Larsson, M. K. ; Faka, A. ; Bhat, M. ; Imbeault, S. ; Goiny, M. ; Orhan, F. ; Oliveros, A. ; Ståhl, S. ; Liu, X. C. ; Choi, Doo Sup ; Sandberg, K. ; Engberg, G. ; Schwieler, L. ; Erhardt, S. / Repeated LPS Injection Induces Distinct Changes in the Kynurenine Pathway in Mice. In: Neurochemical Research. 2016 ; pp. 1-13.
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