Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.
Brain, Behavior, and Immunity. 2014-10-01; 41: 10-21
DOI: 10.1016/j.bbi.2014.03.012
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1. Brain Behav Immun. 2014 Oct;41:10-21. doi: 10.1016/j.bbi.2014.03.012. Epub 2014
Mar 27.
Diet-induced obesity progressively alters cognition, anxiety-like behavior and
lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine
2,3-dioxygenase activation.
André C(1), Dinel AL(1), Ferreira G(1), Layé S(1), Castanon N(2).
Author information:
(1)INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux,
France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286,
33076 Bordeaux, France.
(2)INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux,
France; Université de Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286,
33076 Bordeaux, France. Electronic address: .
Obesity is associated with a high prevalence of mood symptoms and cognitive
dysfunctions that emerges as significant risk factors for important health
complications such as cardiovascular diseases and type 2 diabetes. It is
therefore important to identify the dynamic of development and the
pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity
is also associated with peripheral low-grade inflammation and increased
susceptibility to immune-mediated diseases. Excessive production of
proinflammatory cytokines and the resulting activation of the brain tryptophan
catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote
neurobehavioral complications, particularly depression. In that context,
questions arise about the impact of diet-induced obesity on the onset of
neuropsychiatric alterations and the increased susceptibility to immune-mediated
diseases displayed by obese patients, particularly through brain IDO activation.
To answer these questions, we used C57Bl/6 mice exposed to standard diet or
western diet (WD; consisting of palatable energy-dense food) since weaning and
for 20 weeks. We then measured inflammatory and behavioral responses to a
systemic immune challenge with lipopolysaccharide (LPS) in experimental
conditions known to alter cognitive and emotional behaviors independently of any
motor impairment. We first showed that in absence of LPS, 9 weeks of WD is
sufficient to impair spatial recognition memory (in the Y-maze). On the other
hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze),
but did not affect depressive-like behavior (in the tail-suspension and
forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like
behavior compared to LPS-treated lean mice and exacerbated hippocampal and
hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken
together, these results show that WD exposure alters cognition and anxiety in
unstimulated conditions and enhances activation of neurobiological mechanisms
underlying depression after immune stimulation. They suggest therefore that
obesity, and possibly obesity-associated inflammatory priming, may represent a
vulnerability state to immune-mediated depressive symptoms.
Copyright © 2014 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.bbi.2014.03.012
PMID: 24681251 [Indexed for MEDLINE]