Cognitive and emotional alterations are related to hippocampal inflammation in a mouse model of metabolic syndrome

• Published in: PloS one 2011-09, Vol.6 (9), p.e24325-e24325
• Main Authors: Dinel, Anne-Laure, André, Caroline, Aubert, Agnès, Ferreira, Guillaume, Layé, Sophie, Castanon, Nathalie
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Anxiety; Anxiety - complications; Behavior; Behavior, Animal - physiology; Biology; Brain; Brain-derived neurotrophic factor; Cellular Biology; Cognition; Cognitive ability; Complications; Cytokines; Diabetes; Diabetes mellitus; Disease Models, Animal; Emotional behavior; Emotions; Hippocampus; Hippocampus - metabolism; Hippocampus - physiopathology; Hyperglycemia; Hypothalamus; Inflammation; Inflammation - metabolism; Inflammation - physiopathology; Influence; Insulin; Interleukin 6; Interleukins; Life Sciences; Male; Medicine; Memory; Memory Disorders - complications; Memory tasks; Metabolic disorders; Metabolic syndrome; Metabolic Syndrome - complications; Metabolic Syndrome - metabolism; Metabolic Syndrome - physiopathology; Mice; Nutrition; Obesity; Object recognition; Pathogenesis; Pattern recognition; Peripheral Nervous System - metabolism; Peripheral Nervous System - physiopathology; Plasma levels; Signal transduction; Spatial analysis; Spatial memory; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Type 2 diabetes
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0024325

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.