PMID- 24485475
OWN - NLM
STAT- MEDLINE
DCOM- 20141009
LR  - 20171116
IS  - 1873-3360 (Electronic)
IS  - 0306-4530 (Linking)
VI  - 40
DP  - 2014 Feb
TI  - Lipopolysaccharide-induced brain activation of the indoleamine 2,3-dioxygenase 
      and depressive-like behavior are impaired in a mouse model of metabolic syndrome.
PG  - 48-59
LID - S0306-4530(13)00397-1 [pii]
LID - 10.1016/j.psyneuen.2013.10.014 [doi]
AB  - 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 
      mug/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-1beta, tumor necrosis factor-alpha). 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.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Dinel, Anne-Laure
AU  - Dinel AL
AD  - INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; 
      University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France.
FAU - Andre, Caroline
AU  - Andre C
AD  - University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France; Inserm, Neurocentre Magendie, Physiology of Neuronal 
      Plasticity, U862, 33076 Bordeaux, France.
FAU - Aubert, Agnes
AU  - Aubert A
AD  - INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; 
      University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France.
FAU - Ferreira, Guillaume
AU  - Ferreira G
AD  - INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; 
      University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France.
FAU - Laye, Sophie
AU  - Laye S
AD  - INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; 
      University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France.
FAU - Castanon, Nathalie
AU  - Castanon N
AD  - INRA, Nutrition and Integrative Neurobiology, UMR 1286, 33076 Bordeaux, France; 
      University of Bordeaux, Nutrition and Integrative Neurobiology, UMR 1286, 33076 
      Bordeaux, France. Electronic address: nathalie.castanon@bordeaux.inra.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131101
PL  - England
TA  - Psychoneuroendocrinology
JT  - Psychoneuroendocrinology
JID - 7612148
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Receptors, Leptin)
RN  - 0 (leptin receptor, mouse)
RN  - 343-65-7 (Kynurenine)
RN  - 8DUH1N11BX (Tryptophan)
SB  - IM
MH  - Animals
MH  - Behavior, Animal/*drug effects
MH  - Brain/*drug effects/metabolism
MH  - Depression/*chemically induced/metabolism
MH  - Disease Models, Animal
MH  - Enzyme Activation/drug effects
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*metabolism
MH  - Kynurenine/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Metabolic Syndrome/genetics/*metabolism/pathology/*psychology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred NOD
MH  - Mice, Transgenic
MH  - Receptors, Leptin/genetics
MH  - Tryptophan/metabolism
OTO - NOTNLM
OT  - Cytokines
OT  - Depression
OT  - Forced swim test
OT  - Hippocampus
OT  - Indoleamine 2,3-dioxygenase
OT  - Lipopolysaccharide
OT  - Metabolic syndrome
OT  - db/db mice
EDAT- 2014/02/04 06:00
MHDA- 2014/10/10 06:00
CRDT- 2014/02/04 06:00
PHST- 2013/07/10 00:00 [received]
PHST- 2013/10/24 00:00 [revised]
PHST- 2013/10/24 00:00 [accepted]
PHST- 2014/02/04 06:00 [entrez]
PHST- 2014/02/04 06:00 [pubmed]
PHST- 2014/10/10 06:00 [medline]
AID - S0306-4530(13)00397-1 [pii]
AID - 10.1016/j.psyneuen.2013.10.014 [doi]
PST - ppublish
SO  - Psychoneuroendocrinology. 2014 Feb;40:48-59. doi: 10.1016/j.psyneuen.2013.10.014. 
      Epub 2013 Nov 1.