ArticleThe Journal of clinical investigation2020
Impaired hypocretin/orexin system alters responses to salient stimuli in obese male mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
12 citing papers in PubMed, 27 citations in OpenAlex.
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- Multiomics integration reveals the effect of Orexin A on glioblastoma.Frontiers in pharmacology · 2023Article
- From Molecule to Behavior: Hypocretin/orexin Revisited From a Sex-dependent Perspective.Endocrine reviews · 2022Review
- Dietary intervention improves health metrics and life expectancy of the genetically obese Titan mouse.Communications biology · 2022Article
- Hypothalamic deep brain stimulation as a strategy to manage anxiety disorders.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Insulin-like growth factor I mitigates post-traumatic stress by inhibiting AMP-kinase in orexin neurons.Molecular psychiatry · 2022Article
- Physical Exercise-Induced Astrocytic Neuroprotection and Cognitive Improvement Through Primary Cilia and Mitogen-Activated Protein Kinases Pathway in Rats With Chronic Cerebral Hypoperfusion.Frontiers in aging neuroscience · 2022Article
- Coordination of metabolism, arousal, and reward by orexin/hypocretin neurons.The Journal of clinical investigation · 2020Article
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
The brain has evolved in an environment where food sources are scarce, and foraging for food is one of the major challenges for survival of the individual and species. Basic and clinical studies show that obesity or overnutrition leads to overwhelming changes in the brain in animals and humans. However, the exact mechanisms underlying the consequences of excessive energy intake are not well understood. Neurons expressing the neuropeptide hypocretin/orexin (Hcrt) in the lateral/perifonical hypothalamus (LH) are critical for homeostatic regulation, reward seeking, stress response, and cognitive functions. In this study, we examined adaptations in Hcrt cells regulating behavioral responses to salient stimuli in diet-induced obese mice. Our results demonstrated changes in primary cilia, synaptic transmission and plasticity, cellular responses to neurotransmitters necessary for reward seeking, and stress responses in Hcrt neurons from obese mice. Activities of neuronal networks in the LH and hippocampus were impaired as a result of decreased hypocretinergic function. The weakened Hcrt system decreased reward seeking while altering responses to acute stress (stress-coping strategy), which were reversed by selectively activating Hcrt cells with chemogenetics. Taken together, our data suggest that a deficiency in Hcrt signaling may be a common cause of behavioral changes (such as lowered arousal, weakened reward seeking, and altered stress response) in obese animals.
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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 OpenQuestion graph.