RESUMEN
Previous work has established that the hormone ghrelin engages the hypothalamic-pituitary-adrenal neuroendocrine axis via activation of corticotropin-releasing factor (CRF) neurons of the hypothalamic paraventricular nucleus (PVN). The neuronal circuitry that mediates this effect of ghrelin is currently unknown. Here, we show that ghrelin-induced activation of PVN CRF neurons involved inhibition of γ-aminobutyric acid (GABA) inputs, likely via ghrelin binding sites that were localized at GABAergic terminals within the PVN. While ghrelin activated PVN CRF neurons in the presence of neuropeptide Y (NPY) receptor antagonists or in arcuate nucleus (ARC)-ablated mice, it failed to do it so in mice with ghrelin receptor expression limited to ARC agouti gene related protein (AgRP)/NPY neurons. These data support the notion that ghrelin activates PVN CRF neurons via inhibition of local GABAergic tone, in an ARC-independent manner. Furthermore, these data suggest that the neuronal circuits mediating ghrelin's orexigenic action vs. its role as a stress signal are anatomically dissociated.
Asunto(s)
Núcleo Arqueado del Hipotálamo/efectos de los fármacos , Hormona Liberadora de Corticotropina/metabolismo , Ghrelina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Animales , Arginina/análogos & derivados , Arginina/farmacología , Corticosterona/sangre , Antagonistas del GABA , Técnicas de Silenciamiento del Gen , Ghrelina/administración & dosificación , Infusiones Intraventriculares , Masculino , Ratones , Muscimol/farmacología , Neuropéptido Y/antagonistas & inhibidores , Núcleo Hipotalámico Paraventricular/metabolismo , Receptores de Ghrelina/efectos de los fármacos , Receptores de Ghrelina/genética , Receptores de Ghrelina/metabolismo , Ácido gamma-Aminobutírico/metabolismoRESUMEN
γ-Aminobutyric acid (GABA) is a major inhibitory neurotransmitter in central nervous system, and its application in drugs and functional foods has attracted great attention. To enhance production of γ-aminobutyric acid, Lactobacillus rhamnosus YS9, a strain isolated from Chinese traditional fermented food pickled vegetable, was grown under submerged fermentation. Its cultivation conditions were investigated. When culture pH condition was adjusted to the optimal pH of glutamate decarboxylase activity, culture of Lb. rhamnosus YS9 in medium supplemented with 200 mM of monosodium glutamate and 200 µM of pyridoxal phosphate (PLP), produced 187 mM of GABA.