Is Ghrelin Synthesized in the Central Nervous System?

Cabral, Agustina; Soto, Eduardo Javier López; Epelbaum, Jacques; Perelló, Mario

doi:10.3390/ijms18030638

Cited by 97 publications

(69 citation statements)

References 114 publications

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“…We conclude that ghrelin is absent from the lumbosacral spinal cord. These data, although focused on the caudal spinal cord, are consistent with previous studies that indicate that ghrelin is absent from the CNS (Sakata et al 2009;Furness et al 2011;Kern et al 2014;Cabral et al 2017).…”

Section: Discussionsupporting

confidence: 92%

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Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin

et al. 2017

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In laboratory animals and in human, centrally penetrant ghrelin receptor agonists, given systemically or orally, cause defecation. Animal studies show that the effect is due to activation of ghrelin receptors in the spinal lumbosacral defecation centers. However, it is not known whether there is a physiological role of ghrelin or the ghrelin receptor in the control of defecation. Using immunohistochemistry and immunoassay, we detected and measured ghrelin in the stomach, but were unable to detect ghrelin by either method in the lumbosacral spinal cord, or other regions of the CNS. In rats in which the thoracic spinal cord was transected 5 weeks before, the effects of a ghrelin agonist on colorectal propulsion were significantly enhanced, but defecation caused by water avoidance stress (WAS) was reduced. In knockout rats that expressed no ghrelin and in wild‐type rats, WAS‐induced defecation was reduced by a ghrelin receptor antagonist, to similar extents. We conclude that the ghrelin receptors of the lumbosacral defecation centers have a physiological role in the control of defecation, but that their role is not dependent on ghrelin. This implies that a transmitter other than ghrelin engages the ghrelin receptor or a ghrelin receptor complex.

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Section: Discussionsupporting

confidence: 92%

“…While these observations imply that GHSR1a is in the pathways of defecation control, ghrelin itself is not found in the mouse spinal cord (Furness et al 2011). In fact, it is probable that ghrelin is not present even in other parts of the central nervous system (Sakata et al 2009;Furness et al 2011;Kern et al 2014;Cabral et al 2017).…”

Section: Introductionmentioning

confidence: 90%

Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin

et al. 2017

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“…The circulating ghrelin produced in the stomach and intestines crosses the blood-brain barrier and acts on ARC-POMC neurons (Schaeffer et al 2013). However, it is uncertain whether ghrelin is synthetized at physiologically relevant levels in the central nervous system (Kojima et al 1999;Mondal et al 2005;Cabral et al 2017). We found that ablation of Ghsr1a eliminated the ghrelin-induced excitatory effect on AgRP/NPY neurons, indicating that Ghsr1a is essential for the excitatory effect of ghrelin on AgRP/NPY neurons.…”

Section: Discussionmentioning

confidence: 72%

“…; Cabral et al . ). We found that ablation of Ghsr1a eliminated the ghrelin‐induced excitatory effect on AgRP/NPY neurons, indicating that Ghsr1a is essential for the excitatory effect of ghrelin on AgRP/NPY neurons.…”

Section: Discussionmentioning

confidence: 97%

Ghrelin receptors mediate ghrelin‐induced excitation of agouti‐related protein/neuropeptide Y but not pro‐opiomelanocortin neurons

Chen

Zhou

et al. 2017

Journal of Neurochemistry

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Ghrelin increases food intake and body weight by stimulating orexigenic agouti-related protein (AgRP)/neuropeptide Y (NPY) neurons and inhibiting anorexic pro-opiomelanocortin (POMC) neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type-specific Ghsr-knockout mice. Perforated whole-cell recordings were performed on green fluorescent protein-tagged AgRP/NPY and POMC neurons in the arcuate nucleus in hypothalamic slices. In Ghsr mice, ghrelin (100 nM) significantly increased the firing activity of AgRP/NPY neurons but inhibited the firing activity of POMC neurons. In Ghsr mice, the excitatory effect of ghrelin on AgRP/NPY neurons was abolished. Ablation of Ghsr also eliminated ghrelin-induced increases in the frequency of GABAergic inhibitory postsynaptic currents of POMC neurons. Strikingly, ablation of Ghsr converted the ghrelin effect on POMC neurons from inhibition to excitation. Des-acylated ghrelin had no such effect on POMC neurons in Ghsr mice. In both Ghsr and Ghsr mice, blocking GABA receptors with gabazine increased the basal firing activity of POMC neurons, and ghrelin further increased the firing activity of POMC neurons in the presence of gabazine. Our findings provide unequivocal evidence that Ghsr is essential for ghrelin-induced excitation of AgRP/NPY neurons. However, ghrelin excites POMC neurons through an unidentified mechanism that is distinct from conventional Ghsr.

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“…However, it has been reported that no ghrelin-specific staining is found and ghrelin receptor-expressing neurons do not have adjacent ghrelin immunoreactive terminals in the brain or spinal cord of the rat and mouse [40]. Recently, Cabral et al [41] provided a comprehensive review of all available data related to the distribution of ghrelin in the CNS and concluded that there are no indisputable and reliable evidences to support the idea that ghrelin is present in the brain at physiologically significant levels.…”

Section: Figmentioning

confidence: 99%

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

2018

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Abstract. Ghrelin functions as a neuroprotective agent and saves neurons from various insults include ischemic injury. However, it remains to be elucidated whether ghrelin protects neuronal cells against ischemic injury-induced excessive autophagy. Autophagy is required for the maintenance of neural stem cell homeostasis. However, regarding autophagic cell death, it is commonly assumed that excessive autophagy leads to self-elimination of mammalian cells. The purpose of this study was to investigate the potential neuroprotection effects of ghrelin from excessive autophagy in adult rat hippocampal neural stem cells (NSCs). Oxygen-Glucose Deprivation (OGD) strongly induces autophagy in adult rat hippocampal NSCs. Ghrelin treatment inhibited OGD-induced cell death of adult rat hippocampal NSCs assessed by cell-counting-kit-8 assay. Ghrelin also suppressed OGD-induced excessive autophagy activity. The protective effect of ghrelin was accompanied by an increased expression levels of Bcl-2, p-62 and decreased expression level of LC3-II, Beclin-1 by Western blot. Furthermore, ghrelin reduced autophagosome formation and number of GFP-LC3 transfected puncta. In conclusion, our data suggest that ghrelin protects adult rat hippocampal NSCs from excessive autophagy in experimental stroke (oxygen-glucose deprivation) model. Regulating autophagic activity may be a potential optimizing target for promoting adult rat hippocampal NSCs based therapy for stroke.

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Is Ghrelin Synthesized in the Central Nervous System?

Cited by 97 publications

References 114 publications

Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin

Evidence that central pathways that mediate defecation utilize ghrelin receptors but do not require endogenous ghrelin

Ghrelin receptors mediate ghrelin‐induced excitation of agouti‐related protein/neuropeptide Y but not pro‐opiomelanocortin neurons

Ghrelin protects adult rat hippocampal neural stem cells from excessive autophagy during oxygen-glucose deprivation

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