Differential Expression of PACAP/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors.

Jansen, MI; Musumeci, G; Castorina, A

Differential Expression of PACAP/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors.

Jansen, MI Musumeci, G Castorina, A

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Int J Mol Sci, 2024, 25, (16), pp. 8850
Issue Date:: 2024-08-14

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Field	Value	Language
dc.contributor.author	Jansen, MI
dc.contributor.author	Musumeci, G
dc.contributor.author	Castorina, A https://orcid.org/0000-0001-7037-759X
dc.date.accessioned	2024-10-09T01:10:48Z
dc.date.available	2024-08-12
dc.date.available	2024-10-09T01:10:48Z
dc.date.issued	2024-08-14
dc.identifier.citation	Int J Mol Sci, 2024, 25, (16), pp. 8850
dc.identifier.issn	1422-0067
dc.identifier.issn	1422-0067
dc.identifier.uri	http://hdl.handle.net/10453/181287
dc.description.abstract	Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing-remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors' levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and/or other demyelinating disorders.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation.ispartof	Int J Mol Sci
dc.relation.isbasedon	10.3390/ijms25168850
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0399 Other Chemical Sciences, 0604 Genetics, 0699 Other Biological Sciences
dc.subject.classification	Chemical Physics
dc.subject.classification	3101 Biochemistry and cell biology
dc.subject.classification	3107 Microbiology
dc.subject.classification	3404 Medicinal and biomolecular chemistry
dc.subject.mesh	Humans
dc.subject.mesh	White Matter
dc.subject.mesh	Male
dc.subject.mesh	Multiple Sclerosis
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Pituitary Adenylate Cyclase-Activating Polypeptide
dc.subject.mesh	Adult
dc.subject.mesh	Vasoactive Intestinal Peptide
dc.subject.mesh	Receptors, Vasoactive Intestinal Peptide, Type II
dc.subject.mesh	Aged
dc.subject.mesh	Receptors, Vasoactive Intestinal Polypeptide, Type I
dc.subject.mesh	Autopsy
dc.subject.mesh	Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
dc.subject.mesh	Central Nervous System
dc.subject.mesh	Multiple Sclerosis, Relapsing-Remitting
dc.subject.mesh	Central Nervous System
dc.subject.mesh	Humans
dc.subject.mesh	Multiple Sclerosis
dc.subject.mesh	Multiple Sclerosis, Relapsing-Remitting
dc.subject.mesh	Vasoactive Intestinal Peptide
dc.subject.mesh	Autopsy
dc.subject.mesh	Adult
dc.subject.mesh	Aged
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.subject.mesh	Pituitary Adenylate Cyclase-Activating Polypeptide
dc.subject.mesh	Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
dc.subject.mesh	Receptors, Vasoactive Intestinal Polypeptide, Type I
dc.subject.mesh	Receptors, Vasoactive Intestinal Peptide, Type II
dc.subject.mesh	White Matter
dc.title	Differential Expression of PACAP/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors.
dc.type	Journal Article
utslib.citation.volume	25
utslib.location.activity	Switzerland
utslib.for	0399 Other Chemical Sciences
utslib.for	0604 Genetics
utslib.for	0699 Other Biological Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2024-10-09T01:10:23Z
pubs.issue	16
pubs.publication-status	Published online
pubs.volume	25
utslib.citation.issue	16

Abstract:

Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are two neuroprotective and anti-inflammatory molecules of the central nervous system (CNS). Both bind to three G protein-coupled receptors, namely PAC1, VPAC1 and VPAC2, to elicit their beneficial effects in various CNS diseases, including multiple sclerosis (MS). In this study, we assessed the expression and distribution of PACAP/VIP receptors in the normal-appearing white matter (NAWM) of MS donors with a clinical history of either relapsing-remitting MS (RRMS), primary MS (PPMS), secondary progressive MS (SPMS) or in aged-matched non-MS controls. Gene expression studies revealed MS-subtype specific changes in PACAP and VIP and in the receptors' levels in the NAWM, which were partly corroborated by immunohistochemical analyses. Most PAC1 immunoreactivity was restricted to myelin-producing cells, whereas VPAC1 reactivity was diffused within the neuropil and in axonal bundles, and VPAC2 in small vessel walls. Within and around lesioned areas, glial cells were the predominant populations showing reactivity for the different PACAP/VIP receptors, with distinctive patterns across MS subtypes. Together, these data identify the differential expression patterns of PACAP/VIP receptors among the different MS clinical entities. These results may offer opportunities for the development of personalized therapeutic approaches to treating MS and/or other demyelinating disorders.

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http://hdl.handle.net/10453/181287