ArticleScience advances2016
A novel GABA-mediated corticotropin-releasing hormone secretory mechanism in the median eminence.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- Neuroendocrine response to GABA-B receptor agonism in alcohol-dependent individuals: Results from a combined outpatient and human laboratory experiment.Neuropharmacology · 2018Trial
- Chloride homeostasis dysfunction drives hyperactivation of corticotropin-releasing factor-expressing neurons in the amygdala in stress-induced hypertension.The Journal of clinical investigation · 2026Article
- Corticotropin-releasing factor as a regulator of adrenal glucocorticoid synthesis and brain function: a scientific journey of a neuroendocrine physician.Endocrine journal · 2026Article
- Direct Modulation of CRH Nerve Terminal Function by Noradrenaline and Corticosterone.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Association Between Hypnotics and Glycemic Variability Assessed by Continuous Glucose Monitoring Under Real-Life Conditions in Patients With Type 2 Diabetes: A Cross-Sectional Study.Journal of diabetes research · 2025Article
- Subregion-specific transcriptomic profiling of rat brain reveals sex-distinct gene expression impacted by adolescent stress.Neuroscience · 2024Article
- Early establishment of chloride homeostasis in CRH neurons is altered by prenatal stress leading to fetal HPA axis dysregulation.Frontiers in molecular neuroscience · 2024Article
- NKCC1 and KCC2 Chloride Transporters Have Different Membrane Dynamics on the Surface of Hippocampal Neurons.Cells · 2023Article
- Chemogenetic activation of PVN CRH neurons disrupts the estrous cycle and LH dynamics in female mice.Frontiers in endocrinology · 2023Article
- Article
- Robust GABAergic Regulation of the GnRH Neuron Distal Dendron.Endocrinology · 2022Article
- Arcuate AgRP, but not POMC neurons, modulate paraventricular CRF synthesis and release in response to fasting.Cell & bioscience · 2022Article
- Ninjinyoeito improves social behavior disorder in neuropeptide Y deficient zebrafish.Frontiers in pharmacology · 2022Article
- Gut feelings: the microbiota-gut-brain axis on steroids.American journal of physiology. Gastrointestinal and liver physiology · 2022Review
- A subpopulation of agouti-related peptide neurons exciting corticotropin-releasing hormone axon terminals in median eminence led to hypothalamic-pituitary-adrenal axis activation in response to food restriction.Frontiers in molecular neuroscience · 2022Article
- BDNF shifts excitatory-inhibitory balance in the paraventricular nucleus of the hypothalamus to elevate blood pressure.Journal of neurophysiology · 2021Article
- The potential role of stress and sex steroids in heritable effects of sevoflurane†.Biology of reproduction · 2021Review
- Insulin synthesized in the paraventricular nucleus of the hypothalamus regulates pituitary growth hormone production.JCI insight · 2020Article
- Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics.World journal of psychiatry · 2020Review
- GABAergic System in Stress: Implications of GABAergic Neuron Subpopulations and the Gut-Vagus-Brain Pathway.Neural plasticity · 2020Review
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Corticotropin-releasing hormone (CRH), which is synthesized in the paraventricular nucleus (PVN) of the hypothalamus, plays an important role in the endocrine stress response. The excitability of CRH neurons is regulated by γ-aminobutyric acid (GABA)-containing neurons projecting to the PVN. We investigated the role of GABA in the regulation of CRH release. The release of CRH was impaired, accumulating in the cell bodies of CRH neurons in heterozygous GAD67-GFP (green fluorescent protein) knock-in mice (GAD67(+/GFP)), which exhibited decreased GABA content. The GABAA receptor (GABAAR) and the Na(+)-K(+)-2Cl(-) cotransporter (NKCC1), but not the K(+)-Cl(-) cotransporter (KCC2), were expressed in the terminals of the CRH neurons at the median eminence (ME). In contrast, CRH neuronal somata were enriched with KCC2 but not with NKCC1. Thus, intracellular Cl(-) concentrations ([Cl(-)]i) may be increased at the terminals of CRH neurons compared with concentrations in the cell body. Moreover, GABAergic terminals projecting from the arcuate nucleus were present in close proximity to CRH-positive nerve terminals. Furthermore, a GABAAR agonist increased the intracellular calcium (Ca(2+)) levels in the CRH neuron terminals but decreased the Ca(2+) levels in their somata. In addition, the increases in Ca(2+) concentrations were prevented by an NKCC1 inhibitor. We propose a novel mechanism by which the excitatory action of GABA maintains a steady-state CRH release from axon terminals in the ME.
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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.