ArticleMolecular psychiatry2017
Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice.
Article in Molecular psychiatry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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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.
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
52 citing papers in PubMed, 96 citations in OpenAlex.
- Selective and differential roles of PVHNature communications · 2026Article
- Approach-Avoidance Conflict Paradigms in Animal and Human Studies of Anxiety-A Narrative Review.Behavioral sciences (Basel, Switzerland) · 2025Review
- State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis.Nature metabolism · 2025Article
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- Cortical arealization of interneurons defines shared and distinct molecular programs in developing human and macaque brains.Nature communications · 2025Article
- Chemogenetic inhibition of central amygdala CRF-expressing neurons decreases alcohol intake but not trauma-related behaviors in a rat model of post-traumatic stress and alcohol use disorder.Molecular psychiatry · 2024Article
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- Research Progress of Central and Peripheral Corticotropin-Releasing Hormone in Irritable Bowel Syndrome with Comorbid Dysthymic Disorders.Gut and liver · 2024Review
- GPR55 activation improves anxiety- and depression-like behaviors of mice during methamphetamine withdrawal.Heliyon · 2024Article
- Metabolic and behavioral alterations associated with viral vector-mediated toxicity in the paraventricular hypothalamic nucleus.Bioscience reports · 2024Article
- Hypothalamic CRH neurons represent physiological memory of positive and negative experience.Nature communications · 2023Article
- Local production of corticotropin-releasing hormone in prefrontal cortex modulates male-specific novelty exploration.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Mitochondrial stress-induced GFRAL signaling controls diurnal food intake and anxiety-like behavior.Life science alliance · 2022Article
- The Central Nervous Mechanism of Stress-Promoting Cancer Progression.International journal of molecular sciences · 2022Review
- A hypothalamic dopamine locus for psychostimulant-induced hyperlocomotion in mice.Nature communications · 2022Article
- Formation of False Context Fear Memory Is Regulated by Hypothalamic Corticotropin-Releasing Factor in Mice.International journal of molecular sciences · 2022Article
- RORγt-Expressing Pathogenic CD4Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Article
- Loss of liver X receptor β in astrocytes leads to anxiety-like behaviors via regulating synaptic transmission in the medial prefrontal cortex in mice.Molecular psychiatry · 2021Article
- Effects of Growth Hormone Receptor Ablation in Corticotropin-Releasing Hormone Cells.International journal of molecular sciences · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 6 institutions in 3 countries.
Funding
Abstract
A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, whereas extra-hypothalamic CRH has a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma adrenocorticotropic hormone, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open-field, elevated plus maze, holeboard, light-dark box and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation.
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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.