Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse extended amygdala, hippocampus and hypothalamus, that parallel the expression of depressive-like behavior

François Frenois, Maïté Moreau, Jason O’Connor, Marc Lawson, Charlotte Micon, Jacques Lestage, Keith W. Kelley, Robert Dantzer, Nathalie Castanon
Psychoneuroendocrinology. 2007-06-01; 32(5): 516-531
DOI: 10.1016/j.psyneuen.2007.03.005

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1. Psychoneuroendocrinology. 2007 Jun;32(5):516-31. Epub 2007 May 4.

Lipopolysaccharide induces delayed FosB/DeltaFosB immunostaining within the mouse
extended amygdala, hippocampus and hypothalamus, that parallel the expression of
depressive-like behavior.

Frenois F(1), Moreau M, O’Connor J, Lawson M, Micon C, Lestage J, Kelley KW,
Dantzer R, Castanon N.

Author information:
(1)Integrative Immunology and Behavior Program, University of Illinois at
Urbana-Champaign, 212 Edward R. Madigan Laboratory, 1201 West Gregory Drive,
Urbana, IL 61801, USA.

Proinflammatory cytokines induce both sickness behavior and depression, but their
respective neurobiological correlates are still poorly understood. The aim of the
present study was therefore to identify in mice the neural substrates of sickness
and depressive-like behavior induced by lipopolysaccharide (LPS, 830 microg/kg,
intraperitoneal). LPS-induced depressive-like behavior was dissociated from
LPS-induced sickness by testing mice either at 6 h (at which time sickness was
expected to be maximal) or at 24 h post-LPS (at which time sickness was expected
to be minimal and not to bias the measurement of depressive-like behavior).
Concurrently, the expression of acute and chronic cellular reactivity markers
(c-Fos and FosB/DeltaFosB, respectively) was mapped by immunohistochemistry at
these two time points. In comparison to saline, LPS decreased motor activity in a
new cage at 6 h but not at 24 h. In contrast, the duration of immobility in the
tail suspension test was increased at both 6 and 24 h. This dissociation between
decreased motor activity and depressive-like behavior was confirmed at 24 h
post-LPS in the forced swim test. LPS also decreased sucrose consumption at 24
and 48 h, despite normal food and water consumption by that time. At 24 h
post-LPS, LPS-induced depressive-like behavior was associated with a delayed
cellular activity (as assessed by FosB/DeltaFosB immunostaining) in specific
brain structures, particularly within the extended amygdala, hippocampus and
hypothalamus, whereas c-Fos labeling was markedly decreased by that time in all
the brain areas at 6 h post-LPS. These results provide the first evidence in
favor of a functional dissociation between the brain structures that underlie
cytokine-induced sickness behavior and cytokine-induced depressive-like behavior,
and provide important cues about the neuroanatomical brain circuits through which
cytokines could have an impact on affect.

DOI: 10.1016/j.psyneuen.2007.03.005
PMCID: PMC1978247
PMID: 17482371 [Indexed for MEDLINE]

Auteurs Bordeaux Neurocampus