ArticleMolecular psychiatry2022
High-fat diet induces depression-like phenotype via astrocyte-mediated hyperactivation of ventral hippocampal glutamatergic afferents to the nucleus accumbens.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Transsynaptic neural circuit mapping of ventral hippocampus motivational control systems.Brain structure & function · 2026Article
- Aspirin alleviates long-term high-fat diet-induced depressive-like behavior in male mice via suppressing arachidonic acid-mediated microglial activation and neuroinflammation.Molecular psychiatry · 2026Article
- The role of metabolic disorders in major depressive disorder.Molecular biology reports · 2026Review
- Neurobiology of co-morbid stress and a western diet in mice: mitochondrial, proteomic and behavioral outcomes.Metabolic brain disease · 2026Article
- ATP Release Deficiency through Astrocytic Connexin 43 in the Dorsal Hippocampus Promotes Depressive- and Anxiety-Like Behaviors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- From metabolism to mood regulation: astrocytes as a driver of depression.Frontiers in cellular neuroscience · 2026Review
- Liraglutide improves depressive and cognitive deficits in a high-fat diet rat model of obesity: the role of hippocampal autophagy and the PI3K/Akt/mTOR pathway.Psychopharmacology · 2025Article
- Microglial Feimin Alleviates Cognitive Impairment in High-Fat Diet-Fed Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Investigating the visceral adiposity-major depressive disorder link: a cross-sectional NHANES 2011-2014 analysis and Mendelian randomization study.Eating and weight disorders : EWD · 2025Article
- Astrocytes in maintaining neuronal health and brain function: interplay of aging, diet, and environment.Metabolic brain disease · 2025Review
- Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2025Review
- Feeding the mood: The role of macronutrients in depression prevention and treatment.World journal of psychiatry · 2025Review
- Effects of Lactation Lactoferrin Deficiency on Intestinal Microbiota in Different Mice Models.Nutrients · 2025Article
- Astrocytes of the hippocampus and responses to periprandial neuroendocrine hormones.Physiology & behavior · 2025Review
- Visceral adipose tissue-derived extracellular vesicles promote stress susceptibility in obese mice via miR-140-5p.Acta pharmacologica Sinica · 2025Article
- Excitatory Amino Acid Transporters as Therapeutic Targets in the Treatment of Neurological Disorders: Their Roles and Therapeutic Prospects.Neurochemical research · 2025Review
- Dopamine D1 receptor agonist alleviates post-weaning isolation-induced neuroinflammation and depression-like behaviors in female mice.Behavioral and brain functions : BBF · 2025Article
- Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption, via hippocampal thyroid hormone signaling.Molecular metabolism · 2024Article
- The WFS1-ZnT3-ZnAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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8 authors at 3 institutions in 1 country.
Funding
Abstract
Comorbidity exists between metabolic disorders and depressive syndrome with unclear mechanisms. To characterize the causal relationship, we adopted a 12-week high-fat diet (HFD) to induce metabolic disorder and depressive phenotypes in mice. Initially, we identified an enhanced glutamatergic input in the nucleus accumbens of HFD mice. Retrograde tracing and chemogenetic inhibition showed that the hyperactive ventral hippocampal glutamatergic afferents to the nucleus accumbens determined the exhibition of depression-like behavior in HFD mice. Using lentiviral knockdown and overexpression approaches, we proved that HFD-induced downregulation of glial glutamate transporters, GLAST and GLT-1, contributed to the observed circuit maladaptations and subsequent depression-like behaviors. Finally, we identified a potential therapeutic agent, riluzole, which could mitigate the HFD-induced behavioral deficits by normalizing the expressions of GLAST and GLT-1 and ventral hippocampal glutamatergic afferents to the nucleus accumbens. Overall, astrocyte-mediated disturbance in glutamatergic transmission underlies the metabolic disorder-related depressive syndrome and represents a therapeutic target for this subtype of depressive mood disorders.
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