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Article Dans Une Revue Molecular Neurobiology Année : 2014

Hippocampal GSK3β as a Molecular Link Between Obesity and Depression.

Résumé

Obesity is considered as a risk factor for mood disorders including depression. Nevertheless, the mechanisms underlying this association are not clearly understood. To address this issue, we investigated the impact of high-fat (HF)-diet-induced obesity on depressive-like behavior and on serotonin (5-HT)-dependent Akt/glycogen synthase kinase 3β (GSK3β) signaling in the dentate gyrus (DG) of the hippocampus, which has been associated with mood regulation. We first showed that a HF diet induced significant overweight and hyperglycemia as well as a depressive-like behavior in adult Wistar rats. By using an ex vivo approach on brain slices, we demonstrated that 5-HT activates the Akt/GSK3β cascade in the DG of control chow (C) diet-fed animals and that a 16-week HF diet feeding abolishes this activation, concurrently with a desensitization of leptin and insulin signaling in the same region. Furthermore, depressive-like behavior inversely correlated with 5-HT-induced phosphorylation of GSK3β in the subgranular neurons of the DG. Interestingly, a substitution of HF with C diet for 6 weeks induced a total loss of depressive symptoms, whereas body weight and glycemia remained significantly higher compared to control rats. In addition, food restoration led to a recovery of the Akt/GSK3β signaling pathway activation in the DG. In parallel, we observed a negative correlation between body weight and cell proliferation in the subgranular zone of the DG. To conclude, we provide evidence for a desensitization of 5-HT-induced Akt/GSK3β signaling and an impaired cell proliferation in the DG by HF diet, suggesting novel molecular mechanisms linking obesity to depression.
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Dates et versions

hal-01179285 , version 1 (22-07-2015)

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Ioannis K. Papazoglou, Arnaud Jean, Arieh Gertler, Mohammed Taouis, Claire-Marie Vacher. Hippocampal GSK3β as a Molecular Link Between Obesity and Depression.. Molecular Neurobiology, 2014, 52, pp.363-374. ⟨10.1007/s12035-014-8863-x⟩. ⟨hal-01179285⟩
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