ArticleMolecular neurobiology2015
Hippocampal GSK3β as a Molecular Link Between Obesity and Depression.
Article in Molecular neurobiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Gut-brain axis as a bridge in obesity and depression: Mechanistic exploration and therapeutic prospects.World journal of psychiatry · 2025Article
- Impact of Serotonin Transporter Absence on Brain Insulin Receptor Expression, Plasma Metabolome Changes, and ADHD-like Behavior in Mice fed a Western Diet.Biomolecules · 2024Article
- The Possible Neuroprotective Effect of Caffeic Acid on Cognitive Changes and Anxiety-Like Behavior Occurring in Young Rats Fed on High-Fat Diet and Exposed to Chronic Stress: Role of β-Catenin/GSK-3B Pathway.Journal of molecular neuroscience : MN · 2024Article
- Insulin modulates emotional behavior through a serotonin-dependent mechanism.Molecular psychiatry · 2024Article
- Neuronal Nitric Oxide Synthase Regulates Depression-like Behaviors in Shortening-Induced Obese Mice.Nutrients · 2022Article
- Oxidative Stress-Induced Damage to the Developing Hippocampus Is Mediated by GSK3β.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- The Effects of Brain Serotonin Deficiency on Responses to High Fat Diet in Female Mice.Frontiers in neuroscience · 2021Article
- Downregulation of hippocampal SIRT6 activates AKT/CRMP2 signaling and ameliorates chronic stress-induced depression-like behavior in mice.Acta pharmacologica Sinica · 2020Article
- Depression with Comorbid Diabetes: What Evidence Exists for Treatments Using Traditional Chinese Medicine and Natural Products?Frontiers in pharmacology · 2020Review
- GSK-3β Contributes to Parkinsonian Dopaminergic Neuron Death: Evidence From Conditional Knockout Mice and Tideglusib.Frontiers in molecular neuroscience · 2020Article
- Metformin Promotes Anxiolytic and Antidepressant-Like Responses in Insulin-Resistant Mice by Decreasing Circulating Branched-Chain Amino Acids.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- Selective inhibition of intestinal 5-HT improves neurobehavioral abnormalities caused by high-fat diet mice.Metabolic brain disease · 2019Article
- Insulin Resistance as a Shared Pathogenic Mechanism Between Depression and Type 2 Diabetes.Frontiers in psychiatry · 2019Review
- Brain 5-HT Deficiency Prevents Antidepressant-Like Effects of High-Fat-Diet and Blocks High-Fat-Diet-Induced GSK3β Phosphorylation in the Hippocampus.Frontiers in molecular neuroscience · 2019Article
- SB203580 reverses memory deficits and depression-like behavior induced by microinjection of AβMetabolic brain disease · 2017Article
- Kinoscope: An Open-Source Computer Program for Behavioral Pharmacologists.Frontiers in behavioral neuroscience · 2017Article
- High-fat diet-induced metabolic disorders impairs 5-HT function and anxiety-like behavior in mice.British journal of pharmacology · 2016Article
- Obesity and Its Potential Effects on Antidepressant Treatment Outcomes in Patients with Depressive Disorders: A Literature Review.International journal of molecular sciences · 2016Review
- Potential Roles of Adropin in Central Nervous System: Review of Current Literature.Frontiers in molecular biosciences · 2016Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.