Lipopolysaccharide-induced brain activation of the indoleamine 2,3-dioxygenase and depressive-like behavior are impaired in a mouse model of metabolic syndrome.
Psychoneuroendocrinology. 2014-02-01; 40: 48-59
DOI: 10.1016/j.psyneuen.2013.10.014
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1. Psychoneuroendocrinology. 2014 Feb;40:48-59. doi: 10.1016/j.psyneuen.2013.10.014.
Epub 2013 Nov 1.
Lipopolysaccharide-induced brain activation of the indoleamine 2,3-dioxygenase
and depressive-like behavior are impaired in a mouse model of metabolic syndrome.
Dinel AL(1), André C(2), Aubert A(1), Ferreira G(1), Layé S(1), Castanon N(3).
Author information:
(1)INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux,
France; University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286,
33076 Bordeaux, France.
(2)University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286,
33076 Bordeaux, France; Inserm, Neurocentre Magendie, Physiology of Neuronal
Plasticity, U862, 33076 Bordeaux, France.
(3)INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux,
France; University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286,
33076 Bordeaux, France. Electronic address: .
Although peripheral low-grade inflammation has been associated with a high
incidence of mood symptoms in patients with metabolic syndrome (MetS), much less
is known about the potential involvement of brain activation of cytokines in that
context. Recently we showed in a mouse model of MetS, namely the db/db mice, an
enhanced hippocampal inflammation associated with increased anxiety-like behavior
(Dinel et al., 2011). However, depressive-like behavior was not affected in db/db
mice. Based on the strong association between depressive-like behavior and
cytokine-induced brain activation of indoleamine 2,3-dioxygenase (IDO), the
enzyme that metabolizes tryptophan along the kynurenine pathway, these results
may suggest an impairment of brain IDO activation in db/db mice. To test this
hypothesis, we measured the ability of db/db mice and their healthy db/+
littermates to enhance brain IDO activity and depressive-like behavior after a
systemic immune challenge with lipopolysaccharide (LPS). Here we show that LPS (5
μg/mouse) significantly increased depressive-like behavior (increased immobility
time in a forced-swim test, FST) 24h after treatment in db/+ mice, but not in
db/db mice. Interestingly, db/db mice also displayed after LPS treatment blunted
increase of brain kynurenine/tryptophan ratio compared to their db/+
counterparts, despite enhanced induction of hippocampal cytokine expression
(interleukin-1β, tumor necrosis factor-α). Moreover, this was associated with an
impaired effect of LPS on hippocampal expression of the brain-derived
neurotrophic factor (BDNF) that contributes to mood regulation, including under
inflammatory conditions. Collectively, these data indicate that the rise in brain
tryptophan catabolism and depressive-like behavior induced by innate immune
system activation is impaired in db/db mice. These findings could have relevance
in improving the management and treatment of inflammation-related complications
in MetS.
Copyright © 2013 Elsevier Ltd. All rights reserved.
DOI: 10.1016/j.psyneuen.2013.10.014
PMID: 24485475 [Indexed for MEDLINE]