ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2024
Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Cardiopulmonary crosstalk in Long COVID: a systematic review of emerging evidence.BMC cardiovascular disorders · 2025Pooled it
- Article
- Astrocytic FDX1 Contributes to Copper Dyshomeostasis-associated Synaptic Dysfunction in Depression and Is Modulated by Exercise.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Estrogen Replacement Therapy in Ovariectomized Rats: Complementary Roles of ER and GPR30 in Alleviating Depressive-like Behavior.Current issues in molecular biology · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- Electroacupuncture alleviates depression and gastrointestinal dysfunction by rebalancing GABAergic activity in the central amygdala.World journal of psychiatry · 2026Article
- From energy metabolism to mood regulation: The rise of lactate as a therapeutic target.Journal of advanced research · 2026Review
- Flipping the Switch: MeCP2-Mediated Lactylation Rewires Microglial Metabolism and Inflammation via the HK2/mTOR Axis in Poststroke Neuroinflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- TLR4 and RB1 as the Identified Lactate-Related Genes to Predict the Diagnostic Performance, Gene Regulatory Network, and Targeting Drugs in Depression.Human mutation · 2026Article
- Lactate and cognition: a dual modulator.Frontiers in molecular neuroscience · 2026Review
- Mitochondrial CISD1 Modulates Microglial Metabolic Reprogramming to Drive Stress Susceptibility in Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Beyond Fuel: Exercise-Induced Lactate as a Metabolic-Epigenetic Regulator in Central Nervous System Health and Disease.Biomolecules · 2025Review
- Central neuropeptides as key modulators of astrocyte function in neurodegenerative and neuropsychiatric disorders.Psychopharmacology · 2025Review
- Nose-to-Brain Delivery of Chlorella vulgaris Extracellular Vesicles for Antidepressant Effects.Journal of extracellular vesicles · 2025Article
- The Ferroptosis-Mitochondrial Axis in Depression: Unraveling the Feedforward Loop of Oxidative Stress, Metabolic Homeostasis Dysregulation, and Neuroinflammation.Antioxidants (Basel, Switzerland) · 2025Review
- Chronic mild stress exacerbates atrial fibrillation and neutrophil extracellular traps formation through S100A8/A9 signaling.Signal transduction and targeted therapy · 2025Article
- Depression and anxiety in inflammatory bowel disease: mechanisms and emerging therapeutics targeting the microbiota-gut-brain axis.Frontiers in immunology · 2025Review
- A surface-based cross-sectional fMRI study on brain function differences between comorbid mild or moderate depression and insomnia.Frontiers in neuroscience · 2025Article
- Hypocretin: a promising target for the regulation of homeostasis.Frontiers in neuroscience · 2025Review
- Hypocretin-1/Hypocretin Receptor 1 Regulates Neuroplasticity and Cognitive Function through Hippocampal Lactate Homeostasis in Depressed Model.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
Cognitive dysfunction is not only a common symptom of major depressive disorder, but also a more common residual symptom after antidepressant treatment and a risk factor for chronic and recurrent disease. The disruption of hypocretin regulation is known to be associated with depression, however, their exact correlation is remains to be elucidated. Hypocretin-1 levels are increased in the plasma and hypothalamus from chronic unpredictable mild stress (CUMS) model mice. Excessive hypocretin-1 conducted with hypocretin receptor 1 (HCRTR1) reduced lactate production and brain-derived neurotrophic factor (BDNF) expression by hypoxia-inducible factor-1α (HIF-1α), thus impairing adult hippocampal neuroplasticity, and cognitive impairment in CUMS model. Subsequently, it is found that HCRTR1 antagonists can reverse these changes. The direct effect of hypocretin-1 on hippocampal lactate production and cognitive behavior is further confirmed by intraventricular injection of hypocretin-1 and microPET-CT in rats. In addition, these mechanisms are further validated in astrocytes and neurons in vitro. Moreover, these phenotypes and changes in molecules of lactate transport pathway can be duplicated by specifically knockdown of HCRTR1 in hippocampal astrocytes. In summary, the results provide molecular and functional insights for involvement of hypocretin-1-HCRTR1 in altered cognitive function in depression.
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Registered trials
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 Socratic graph.