Lipopolysaccharide-induced brain activation of the indoleamine 2,3-dioxygenase and depressive-like behavior are impaired in a mouse model of metabolic syndrome

Anne-Laure Dinel, Caroline André, Agnès Aubert, Guillaume Ferreira, Sophie Layé, Nathalie Castanon
Psychoneuroendocrinology. 2014-02-01; 40: 48-59
DOI: 10.1016/j.psyneuen.2013.10.014

https://www.bordeaux-neurocampus.fr/12036

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.