title: Analysis of brain nuclei accessible to ghrelin present in the cerebrospinal fluid.
abstract: Ghrelin is a stomach-derived peptide hormone that acts in the brain to regulate many important physiological functions. Ghrelin receptor, named the growth hormone secretagogue receptor (GHSR), is present in many brain areas with or without obvious direct access to ghrelin circulating in the bloodstream. Ghrelin is also present in the cerebrospinal fluid (CSF) but the brain targets of CSF ghrelin are unclear. Here, we studied which brain areas are accessible to ghrelin present in the CSF. For this purpose, we centrally injected mice with fluorescein-labeled ghrelin (F-ghrelin) peptide tracer and then systematically mapped the distribution of F-ghrelin signal through the brain. Our results indicated that centrally injected F-ghrelin labels neurons in most of the brain areas where GHSR is present. Also, we detected F-ghrelin uptake in the ependymal cells of both wild-type and GHSR-null mice. We conclude that CSF ghrelin is able to reach most of brain areas expressing GHSR. Also, we propose that the accessibility of CSF ghrelin to the brain parenchyma occurs through the ependymal cells in a GHSR-independent manner.
authors.affiliation: Laboratory of Neurophysiology of the Multidisciplinary Institute of Cell Biology, Argentine Research Council (CONICET) and Scientific Research Commission, La Plata, Province of Buenos Aires (CIC-PBA), Argentina.
authors.forename: A
authors.initials: A
authors.lastname: Cabral
authors.forename: G
authors.initials: G
authors.lastname: Fernandez
authors.forename: M
authors.initials: M
authors.lastname: Perello
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D019793:Fluorescein / Q000493:pharmacokinetics; D054439:Ghrelin / Q000134:cerebrospinal fluid* / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D054439:Ghrelin; D012333:RNA, Messenger; D054440:Receptors, Ghrelin; D019793:Fluorescein
keywords: AHA; AP; ARC; Amb; Ammon’s horn; CA; CSF; DMH; DMV; DR; DVC; EW; Edinger Westphal nucleus; GHSR; ICV; IR; LSD; LoC; MCPC; ME; MPOA; PVH; SCh; SFO; SN; SUM; VTA; acyl-ghrelin; anterior hypothalamic area; antero-posterior; arcuate nucleus; cerebrospinal fluid; dorsal motor nucleus of the vagus; dorsal raphe nucleus; dorsal vagal complex; dorsomedial nucleus; ependymal cells; growth hormone secretagogue receptor; hypothalamus; immunoreactive; intra-cerebro-ventricular; lateral septal nucleus, dorsal part; locus coeruleus; magnocellular nucleus of the posterior commissure; medial preoptic area; median eminence; nucleus ambiguous; paraventricular nucleus; subfornical organ; substantia nigra; suprachiasmatic nucleus; supramammillary nucleus; ventral tegmental area
references.citation: Nat Neurosci. 2008 Jul;11(7):752-3
references.pmid: 18552842
references.citation: Neuroreport. 1996 Dec 20;8(1):373-7
references.pmid: 9051813
references.citation: Science. 1996 Aug 16;273(5277):974-7
references.pmid: 8688086
references.citation: Brain Res. 2008 Feb 27;1196:59-64
references.pmid: 18234162
references.citation: Cell Tissue Res. 2006 Aug;325(2):397-402
references.pmid: 16555054
references.citation: J Comp Neurol. 1997 Aug 11;384(4):556-68
references.pmid: 9259489
references.citation: Biol Psychiatry. 2010 May 1;67(9):880-6
references.pmid: 20034618
references.citation: J Comp Neurol. 2013 Oct 15;521(15):3389-405
references.pmid: 23649873
references.citation: J Med Chem. 2000 Nov 16;43(23):4370-6
references.pmid: 11087562
references.citation: J Neurosci. 2011 Jun 22;31(25):9147-58
references.pmid: 21697366
references.citation: J Clin Endocrinol Metab. 2003 Jun;88(6):2943-6
references.pmid: 12788909
references.citation: Mol Cell Endocrinol. 2011 Jun 20;340(1):80-7
references.pmid: 21354264
references.citation: Biochem Biophys Res Commun. 2002 Dec 20;299(5):739-43
references.pmid: 12470640
references.citation: PLoS One. 2012;7(2):e31462
references.pmid: 22363652
references.citation: Nature. 1999 Dec 9;402(6762):656-60
references.pmid: 10604470
references.citation: Regul Pept. 2011 Dec 10;172(1-3):69-76
references.pmid: 21893106
references.citation: Neuron. 2003 Feb 20;37(4):649-61
references.pmid: 12597862
references.citation: Regul Pept. 2009 Jun 5;155(1-3):91-8
references.pmid: 19361544
references.citation: Physiol Behav. 2011 Nov 30;105(1):43-51
references.pmid: 21513721
references.citation: Cell Metab. 2013 Apr 2;17(4):607-17
references.pmid: 23562080
references.citation: J Comp Neurol. 2010 Apr 1;518(7):943-62
references.pmid: 20127760
references.citation: Physiol Behav. 2006 Aug 30;89(1):71-84
references.pmid: 16859720
references.citation: Mol Cell Endocrinol. 2010 Apr 12;317(1-2):154-60
references.pmid: 20035826
references.citation: J Comp Neurol. 2001 Jan 15;429(3):469-89
references.pmid: 11116232
references.citation: J Clin Invest. 2006 Dec;116(12):3229-39
references.pmid: 17060947
references.citation: J Comp Neurol. 2006 Jan 20;494(3):528-48
references.pmid: 16320257
references.citation: Physiol Rev. 2005 Apr;85(2):495-522
references.pmid: 15788704
references.citation: Neuroendocrinology. 1999 Nov;70(5):306-16
references.pmid: 10567856
references.citation: J Neurosci. 2006 Feb 15;26(7):2022-30
references.pmid: 16481435
references.citation: Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1512-7
references.pmid: 23297228
references.citation: J Neuroendocrinol. 2002 Jun;14(6):429-34
references.pmid: 12047717
references.citation: Regul Pept. 2005 Mar 15;126(1-2):55-9
references.pmid: 15620414
references.citation: J Clin Invest. 2005 Dec;115(12):3564-72
references.pmid: 16322794
references.citation: Neurosci Lett. 2002 Mar 22;321(3):157-60
references.pmid: 11880196
references.citation: J Neuroendocrinol. 2008 Oct;20(10):1138-46
references.pmid: 18673413
references.citation: PLoS One. 2012;7(8):e44089
references.pmid: 22952883
references.citation: J Clin Invest. 2011 Jul;121(7):2684-92
references.pmid: 21701068
references.citation: J Comp Neurol. 2012 Feb 1;520(2):281-94
references.pmid: 21674492
references.citation: Biol Psychiatry. 2012 Sep 1;72(5):347-53
references.pmid: 22458951
references.citation: Neuroscience. 2011 Oct 13;193:1-9
references.pmid: 21835225
references.citation: Peptides. 2010 Apr;31(4):757-76
references.pmid: 20093161
references.citation: Neuropeptides. 2010 Apr;44(2):133-8
references.pmid: 20036003
references.citation: Nat Neurosci. 2006 Mar;9(3):381-8
references.pmid: 16491079
references.citation: Nature. 2001 Jan 11;409(6817):194-8
references.pmid: 11196643
references.citation: Brain Res Mol Brain Res. 1997 Aug;48(1):23-9
references.pmid: 9379845
references.citation: J Pharmacol Exp Ther. 2002 Aug;302(2):822-7
references.pmid: 12130749