Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome.
PLoS ONE. 2011-09-16; 6(9): e24325
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1. PLoS One. 2011;6(9):e24325. doi: 10.1371/journal.pone.0024325. Epub 2011 Sep 16.
Cognitive and emotional alterations are related to hippocampal inflammation in a
mouse model of metabolic syndrome.
Dinel AL(1), André C, Aubert A, Ferreira G, Layé S, Castanon N.
(1)Nutrition et Neurobiologie Intégrée, INRA UMR 1286, Bordeaux, France.
Converging clinical data suggest that peripheral inflammation is likely involved
in the pathogenesis of the neuropsychiatric symptoms associated with metabolic
syndrome (MetS). However, the question arises as to whether the increased
prevalence of behavioral alterations in MetS is also associated with central
inflammation, i.e. cytokine activation, in brain areas particularly involved in
controlling behavior. To answer this question, we measured in a mouse model of
MetS, namely the diabetic and obese db/db mice, and in their healthy db/+
littermates emotional behaviors and memory performances, as well as plasma levels
and brain expression (hippocampus; hypothalamus) of inflammatory cytokines. Our
results shows that db/db mice displayed increased anxiety-like behaviors in the
open-field and the elevated plus-maze (i.e. reduced percent of time spent in
anxiogenic areas of each device), but not depressive-like behaviors as assessed
by immobility time in the forced swim and tail suspension tests. Moreover, db/db
mice displayed impaired spatial recognition memory (hippocampus-dependent task),
but unaltered object recognition memory (hippocampus-independent task). In
agreement with the well-established role of the hippocampus in anxiety-like
behavior and spatial memory, behavioral alterations of db/db mice were associated
with increased inflammatory cytokines (interleukin-1β, tumor necrosis factor-α
and interleukin-6) and reduced expression of brain-derived neurotrophic factor
(BDNF) in the hippocampus but not the hypothalamus. These results strongly point
to interactions between cytokines and central processes involving the hippocampus
as important contributing factor to the behavioral alterations of db/db mice.
These findings may prove valuable for introducing novel approaches to treat
neuropsychiatric complications associated with MetS.
PMID: 21949705 [Indexed for MEDLINE]