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Study M046

Study name

Parrott JM 2016

Title

Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation

Overall design

Here two novel transgenic mouse strains were utilized to directly test the hypothesis that neurotoxic kynurenine metabolism causes depressive-like behavior following peripheral immune activation. Wild-type (WT) or kynurenine 3-monooxygenase (KMO)-deficient (KMO-/-) mice were administered either lipopolysaccharide (LPS, 0.5 mg/kg) or saline. Depressive-like behavior was measured across multiple domains 24 h after immune challenge. Treatment groups: WT and KMO-/- mice were treated (i.p.) with either saline (WT n = 36; KMO-/- n = 24) or LPS (WT n = 37; KMO-/- n = 24). WT and HAAO-/- mice were also treated (i.p.) with either saline (WT n = 26; HAAO-/- n = 29) or LPS (WT n = 29; HAAO-/- n = 31). WT mice were treated (i.p.) with either saline (n = 12) or LPS (n = 12) and brain regions were microdissected at 24 h. Dorsal hippocampus, ventral hippocampus, central amygdala and nucleus accumbens samples were prepared for liquid chromatography/mass spectrometry (LC/MS) and analyzed for kynurenine metabolites as previously described. Only data from WT mouse were used.

Study Type

Type1;

Data available

Unavailable

Organism

Mouse; C57BL/6N mouse;

Categories of depression

Animal model; Lipopolysaccharide induced depression model; Lipopolysaccharide induced depression model;

Criteria for depression

Sucrose preference test, tail suspension test

Sample size

24

Tissue

Peripheral; Blood; Plasma;

Central; Brain; Brain;

Central; Brain; Dorsal hippocampus;

Central; Brain; Ventral hippocampus;

Central; Brain; Central amygdala;

Central; Brain; Nucleus accumbens;

Platform

MS-based; LC-MS: Thermo Fisher Scientific Dionex UltiMate 3000 HPLC with Thermo Fisher Scientific Q Exactive mass spectrometer (Waltham, MA, USA);

PMID

27754481

DOI

10.1038/tp.2016.200

Citation

Parrott JM, Redus L, Santana-Coelho D, et al. Neurotoxic kynurenine metabolism is increased in the dorsal hippocampus and drives distinct depressive behaviors during inflammation. Transl Psychiatry 2016;6(10):e918.

Metabolite

L-Tryptophan;

L-Kynurenine;

Kynurenic acid;

Xanthurenic acid;

Hydroxykynurenine;

3-Hydroxyanthranilic acid;