Localization of the neuropeptides pituitary adenylate cyclase-activating polypeptide, vasoactive intestinal peptide, and their receptors in the basal brain blood vessels and trigeminal ganglion of the mouse CNS; an immunohistochemical study.

CGRP PAC1 PACAP VIP VPAC1 VPAC2 migraine trigeminal ganglion

Journal

Frontiers in neuroanatomy

ISSN: 1662-5129

Titre abrégé: Front Neuroanat

Pays: Switzerland

ID NLM: 101477943

Informations de publication

Date de publication:
2022

Historique:

received: 11 07 2022

accepted: 04 10 2022

entrez: 17 11 2022

pubmed: 18 11 2022

medline: 18 11 2022

Statut: epublish

Résumé

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are structurally related neuropeptides that are widely expressed in vertebrate tissues. The two neuropeptides are pleiotropic and have been associated with migraine pathology. Three PACAP and VIP receptors have been described: PAC1, VPAC1, and VPAC2. The localization of these receptors in relation to VIP and PACAP in migraine-relevant structures has not previously been shown in mice. In the present study, we used fluorescence immunohistochemistry, well-characterized antibodies, confocal microscopy, and three-dimensional reconstruction to visualize the distribution of PACAP, VIP, and their receptors in the basal blood vessels (circle of Willis), trigeminal ganglion, and brain stem spinal trigeminal nucleus (SP5) of the mouse CNS. We demonstrated a dense network of circularly oriented VIP fibers on the basal blood vessels. PACAP nerve fibers were fewer in numbers compared to VIP fibers and ran along the long axis of the blood vessels, colocalized with calcitonin gene-related peptide (CGRP). The nerve fibers expressing CGRP are believed to be sensorial, with neuronal somas localized in the trigeminal ganglion and PACAP was found in a subpopulation of these CGRP-neurons. Immunostaining of the receptors revealed that only the VPAC1 receptor was present in the basal blood vessels, localized on the surface cell membrane of vascular smooth muscle cells and innervated by VIP fibers. No staining was seen for the PAC1, VPAC1, or VPAC2 receptor in the trigeminal ganglion. However, distinct PAC1 immunoreactivity was found in neurons innervated by PACAP nerve terminals located in the spinal trigeminal nucleus. These findings indicate that the effect of VIP is mediated via the VPAC1 receptor in the basal arteries. The role of PACAP in cerebral arteries is less clear. The localization of PACAP in a subpopulation of CGRP-expressing neurons in the trigeminal ganglion points toward a primary sensory function although a dendritic release cannot be excluded which could stimulate the VPAC1 receptor or the PAC1 and VPAC2 receptors on immune cells in the meninges, initiating neurogenic inflammation relevant for migraine pathology.

Identifiants

DOI: 10.3389/fnana.2022.991403 PMID: 36387999 PMC: PMC9643199

pubmed: 36387999

doi: 10.3389/fnana.2022.991403

pmc: PMC9643199

doi:

Types de publication

Journal Article

Langues

eng

Pagination

991403

Informations de copyright

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Références

Neuroscience. 2015 Nov 12;308:144-56

pubmed: 26321242

Front Cell Neurosci. 2021 Jan 15;14:623134

pubmed: 33519387

Cephalalgia. 2017 Feb;37(2):114-124

pubmed: 26994300

Brain. 2009 Jan;132(Pt 1):16-25

pubmed: 19052139

Neuroscience. 1999 Jan;88(1):213-22

pubmed: 10051202

CNS Neurol Disord Drug Targets. 2010 Nov;9(5):661-6

pubmed: 20632962

Cell Tissue Res. 1998 Jan;291(1):65-79

pubmed: 9394044

Cell Tissue Res. 2000 Jan;299(1):59-70

pubmed: 10654070

Br J Pharmacol. 2012 May;166(1):4-17

pubmed: 22289055

Biochim Biophys Acta. 1997 Dec 12;1359(3):250-62

pubmed: 9434131

J Neurosci. 2021 May 26;41(21):4697-4715

pubmed: 33846231

Regul Pept. 1995 Aug 22;58(3):89-98

pubmed: 8577931

J Mol Neurosci. 2008 Nov;36(1-3):270-8

pubmed: 18607779

Cephalalgia. 2010 Oct;30(10):1179-86

pubmed: 20855363

JAMA Netw Open. 2021 Aug 2;4(8):e2118543

pubmed: 34357396

Brain Res. 2000 Jan 24;853(2):186-96

pubmed: 10640616

Exp Brain Res. 2009 Jun;196(1):179-93

pubmed: 19288089

Cureus. 2021 Sep 16;13(9):e18032

pubmed: 34540516

Brain Res. 2015 Mar 10;1600:93-109

pubmed: 25463029

Neuroscience. 1998 Apr;83(4):1261-72

pubmed: 9502264

Biochem Biophys Res Commun. 1989 Oct 16;164(1):567-74

pubmed: 2803320

J Histochem Cytochem. 1994 Dec;42(12):1635-42

pubmed: 7983364

J Neurosci. 1997 Apr 1;17(7):2637-44

pubmed: 9065523

Cephalalgia. 2021 Jan;41(1):33-44

pubmed: 33231489

Neuroscience. 1993 Dec;57(3):725-32

pubmed: 7508577

Brain. 2014 Mar;137(Pt 3):779-94

pubmed: 24501094

Cell Tissue Res. 1991 Jul;265(1):197-201

pubmed: 1913779

Peptides. 2011 Jul;32(7):1439-46

pubmed: 21605612

Eur J Pharmacol. 2011 Nov 16;670(1):186-94

pubmed: 21914446

Neuroreport. 2001 Jul 20;12(10):2215-9

pubmed: 11447337

Front Cell Neurosci. 2019 Mar 28;13:114

pubmed: 30983973

Pharmacol Rev. 2009 Sep;61(3):283-357

pubmed: 19805477

J Headache Pain. 2008 Jun;9(3):151-7

pubmed: 18437288

Cephalalgia. 2020 Oct;40(12):1296-1309

pubmed: 32486909

Peptides. 1985 Jul-Aug;6(4):747-54

pubmed: 2415955

Semin Immunopathol. 2018 May;40(3):229-236

pubmed: 29616309

Neuroscience. 2006 Nov 17;143(1):223-30

pubmed: 16938409

PLoS One. 2017 Nov 20;12(11):e0188166

pubmed: 29155851

J Headache Pain. 2018 Mar 9;19(1):21

pubmed: 29523978

Exp Ther Med. 2019 Aug;18(2):916-925

pubmed: 31384324

J Comp Neurol. 2017 Jun 1;525(8):1934-1961

pubmed: 28160289

Brain. 2022 Jul 29;145(7):2450-2460

pubmed: 35136961

Ann N Y Acad Sci. 1996 Dec 26;805:410-26; discussion 427-8

pubmed: 8993421

J Cereb Blood Flow Metab. 1989 Apr;9(2):204-11

pubmed: 2921295

Regul Pept. 1995 Jan 26;55(2):133-48

pubmed: 7754101

Front Endocrinol (Lausanne). 2020 Jul 14;11:377

pubmed: 32765418

J Neural Transm (Vienna). 2020 Apr;127(4):431-444

pubmed: 32088764

Cell Tissue Res. 1980;208(1):135-42

pubmed: 6771016

J Pharmacol Exp Ther. 2019 Apr;369(1):26-36

pubmed: 30643015

Ann N Y Acad Sci. 2006 Jul;1070:422-6

pubmed: 16888203

J Neuroinflammation. 2011 Feb 28;8:20

pubmed: 21356101

Neuroscience. 1996 Aug;73(4):1049-60

pubmed: 8809823

Brain Res Mol Brain Res. 2002 Aug 15;104(2):137-42

pubmed: 12225867

Cell Tissue Res. 1992 Aug;269(2):275-9

pubmed: 1423494

Neuroreport. 2002 Mar 25;13(4):507-9

pubmed: 11930171

J Mol Neurosci. 2018 Sep;66(1):102-113

pubmed: 30105629

J Cereb Blood Flow Metab. 1988 Oct;8(5):697-712

pubmed: 3417797

Cephalalgia. 2011 Jan;31(2):181-9

pubmed: 20974589

Prog Neurobiol. 1995 Jan;45(1):1-98

pubmed: 7716258

J Cereb Blood Flow Metab. 1993 Mar;13(2):291-7

pubmed: 8436621

J Headache Pain. 2018 Apr 4;19(1):28

pubmed: 29619773

Neuroscience. 2018 Nov 21;393:319-332

pubmed: 30336190

J Cereb Blood Flow Metab. 2000 Aug;20(8):1205-14

pubmed: 10950381

J Pain. 2008 May;9(5):449-56

pubmed: 18337184

J Cereb Blood Flow Metab. 2004 Jun;24(6):628-35

pubmed: 15181370