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

The excitatory action of gamma-aminobutyric-acid (GABA) in the median-eminence (ME) led to the steady-state release of corticotropin-releasing hormone (CRH) from CRH axon terminals, which modulates the hypothalamic-pituitary-adrenal (HPA) axis. However, in ME, the source of excitatory GABAergic inpu...

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Bibliographic Details
Published in:Frontiers in molecular neuroscience 2022-09, Vol.15, p.990803-990803
Main Authors: Yesmin, Ruksana, Watanabe, Miho, Sinha, Adya Saran, Ishibashi, Masaru, Wang, Tianying, Fukuda, Atsuo
Format: Article
Language:English
Subjects:
AgRP neuron
Animals
Arcuate nucleus
Brain
Chloride transport
Corticosterone
Corticotropin-releasing hormone
CRH neuron
Depolarization
Dietary restrictions
Experiments
Food
Food availability
Homeostasis
Hypothalamic-pituitary-adrenal axis
Hypothalamus
Laboratories
median eminence
Neurons
Neuroscience
NKCC1
Paraventricular nucleus
Peptides
Physiology
Pituitary
Presynapse
Stress
γ-Aminobutyric acid
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Summary:The excitatory action of gamma-aminobutyric-acid (GABA) in the median-eminence (ME) led to the steady-state release of corticotropin-releasing hormone (CRH) from CRH axon terminals, which modulates the hypothalamic-pituitary-adrenal (HPA) axis. However, in ME, the source of excitatory GABAergic input is unknown. We examined agouti-related peptide (AgRP) expressing neurons in the arcuate nucleus as a possible source for excitatory GABAergic input. Here, we show that a subpopulation of activated AgRP neurons directly project to the CRH axon terminals in ME elevates serum corticosterone levels in 60% food-restricted mice. This increase in serum corticosterone is not dependent on activation of CRH neuronal soma in the paraventricular nucleus. Furthermore, conditional deletion of Na + -K + -2Cl – cotransporter-1 (NKCC1), which promotes depolarizing GABA action, from the CRH axon terminals results in significantly lower corticosterone levels in response to food restriction. These findings highlight the important role of a subset of AgRP neurons in HPA axis modulation via NKCC1-dependent GABAergic excitation in ME.
ISSN:1662-5099
1662-5099
DOI:10.3389/fnmol.2022.990803