[go: up one dir, main page]
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.1
4.9
Journals
IJMS
Special Issues
Emerging Neuroprotective and Regenerative Strategies for the Treatment of Demyelinating...
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Emerging Neuroprotective and Regenerative Strategies for the Treatment of Demyelinating Disorders of the Central Nervous

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (30 June 2024) | Viewed by 983

Special Issue Editor

Dr. Alessandro Castorina

E-Mail Website
Guest Editor
School of Life Sciences, University of Technology Sydney, Sydney, NSW 2007, Australia
Interests: nervous system diseases; neuropharmacology; anatomy; biomolecular; musculoskeletal disorders; neuropathic pain
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Demyelinating disorders that specifically affect the brain and/or spine in the central nervous system (CNS) are common neurological conditions and can be separated into primary and secondary idiopathic inflammatory-demyelinating diseases (IIDDs). Both groups of IIDDs are characterised by damage to the myelin sheaths covering axons, with the main difference being that in secondary IIDDs, the aetiology is usually well defined (e.g., post-infectious, ischemic, metabolic, or toxic), so therapies targeting the underlying cause can (in most cases) successfully reverse disease progression. In contrast, there is no known cause for primary IIDDs, although growing evidence suggests the contribution of several risk factors (i.e., genetics, environment, life style, diet, etc.) in disease pathogenesis. To date, there is no definitive cure for primary IIDDs; however, there are several disease-modifying therapies able to alter disease progression in some patients and an increasing number of promising therapeutic strategies are currently under scrutiny in preclinical models and in clinical trials. Such emerging therapeutics primarily aim to increase neuroprotection, enhance nerve conduction and/or promote myelin regeneration.

The main scope of the Special Issue is to shed light on the most recent advances on such novel therapeutic strategies for IIDDs, as well as rare demyelinating conditions of the CNS. Special emphasis will be given to contributions focusing on the identification and preclinical validation of targets of potential clinical significance in demyelinating disorders of the CNS, as well as review articles providing updates on emerging treatment options for such devastating pathologies.

Dr. Alessandro Castorina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neuroprotection
  • demyelinating disorders
  • multiple sclerosis
  • optic neuritis
  • transverse myelitis
  • Aicardi–Goutières syndrome
  • acute disseminated encephalomyelitis
  • neuromyelitis optica
  • HTLV-I associated myelopathy
  • Balo’s disease
  • Schilder’s disease

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (1 paper)

Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

24 pages, 16101 KiB  
Article
Differential Expression of PACAP/VIP Receptors in the Post-Mortem CNS White Matter of Multiple Sclerosis Donors
by Margo Iris Jansen, Giuseppe Musumeci and Alessandro Castorina
Int. J. Mol. Sci. 2024, 25(16), 8850; https://doi.org/10.3390/ijms25168850 - 14 Aug 2024
Viewed by 605
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, [...] Read more.
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. Full article
(This article belongs to the Special Issue Emerging Neuroprotective and Regenerative Strategies for the Treatment of Demyelinating Disorders of the Central Nervous)
►▼ Show Figures

Figure 1

Figure 1
<p>Representative lesions and normal-appearing white matter in human brain sections from donors with different MS subtypes. Luxol Fast Blue (LFB) staining shows the intense blue staining of myelinated fibers in the white matter (WM) of (<b>A</b>) non-MS donors, differentiating it from the less myelinated grey matter (GM). Evident discoloring of lesioned areas (indicated by black arrowheads) can be appreciated in sections from (<b>B</b>) RRMS, (<b>C</b>) PPMS and (<b>D</b>) SPMS cases. Myelin is stained blue, resulting in a clear distinction between GM and WM. Scale bar in (<b>A</b>) 200 µm, (<b>B</b>,<b>C</b>) 500 µm, (<b>D</b>) 2000 µm and NAWM (panels on the right) 25 µm. MS = multiple sclerosis, RRMS = relapsing–remitting MS, PPMS = primary-progressive MS, SPMS = secondary-progressive MS, GM = grey matter, WM = white matter.</p> Full article ">Figure 2
<p>Differential expression of PACAP and VIP neuropeptide genes in the normal-appearing white matter of MS donors. (<b>A</b>) PACAP (gene name = ADCYAP1) expression was measured using RT-qPCR, comparing non-MS and MS cases. Further stratification of cases by clinical course, showing the expression levels of ADCYAP1 in (<b>A′</b>) non-MS vs. RRMS, (<b>A″</b>) non-MS vs. PPMS and (<b>A‴</b>) non-MS vs. SPMS. (<b>B</b>) VIP gene expression in non-MS vs. MS cases. A stratification similar to that in A demonstrates relative changes in the transcript levels between non-MS and (<b>B′</b>) RRMS, (<b>B″</b>) PPMS and (<b>B‴</b>) SPMS cases. The data shown are the mean fold change ± SEM, obtained from <span class="html-italic">n</span> = 6 (non-MS), <span class="html-italic">n</span> = 5 (RRMS), <span class="html-italic">n</span> = 6 (SPMS) and <span class="html-italic">n</span> = 4 (PPMS) cases. <span class="html-italic">p</span>-values &gt; 0.05 are also shown. * <span class="html-italic">p</span> &lt; 0.05 or *** <span class="html-italic">p</span> &lt; 0.001 vs. non-MS, as determined by unpaired <span class="html-italic">t</span>-test. VIP = vasoactive intestinal peptide, PACAP = pituitary adenylate cyclase activating polypeptide, MS = multiple sclerosis, NAWM = normal-appearing white matter, RRMS = relapsing–remitting MS, PPMS = primary progressive MS, SPMS = secondary progressive MS.</p> Full article ">Figure 3
<p>Differential expression of PAC1, VPAC1 and VPAC2 genes in the normal-appearing white matter of MS donors. Gene expression of (<b>A</b>) ADCYAP1R1 (aka PAC1), (<b>B</b>) VIPR1 (VPAC1) and (<b>C</b>) VIPR2 (VPAC2) in the NAWM of non-MS vs. MS donors. Upon stratification based on the clinical MS course, the gene expression levels of ADCYAP1R1, VIPR1 and VIPR2 were determined for (<b>A′</b>–<b>C′</b>) RRMS, (<b>A″</b>–<b>C″</b>) PPMS and (<b>A‴</b>–<b>C‴</b>) SPMS cases. The data shown are the mean fold change ± SEM, obtained from <span class="html-italic">n</span> = 6 (non-MS), <span class="html-italic">n</span> = 5 (RRMS), <span class="html-italic">n</span> = 6 (SPMS) and <span class="html-italic">n</span> = 4 (PPMS) cases. <span class="html-italic">p</span>-values &gt; 0.05 are also shown. * <span class="html-italic">p</span> &lt; 0.05 or *** <span class="html-italic">p</span> &lt; 0.001 vs. non-MS, as determined by unpaired <span class="html-italic">t</span>-test. ADCYAP1R1 = Pituitary adenylate cyclase-activating polypeptide type I receptor, VIPR1 = Vasoactive intestinal polypeptide receptor 1, VIPR2 = Vasoactive intestinal polypeptide receptor 2, MS = multiple sclerosis, NAWM = normal-appearing white matter, RRMS = relapsing–remitting MS, PPMS = primary progressive MS, SPMS = secondary progressive MS.</p> Full article ">Figure 4
<p>PAC1 immunoreactivity in the normal-appearing white matter of RRMS, PPMS and SPMS cases. (<b>A</b>) Representative images showing PAC1 immunoreactive cells in the NAWM of MS donors with a clinical history of RRMS, PPMS or SPMS and non-MS control cases. White arrows in each panel point to PAC1<sup>+</sup> cells, which exhibit chromatin-dense and rounded/oval shaped nuclei, consistent with the oligodendrocyte/OPC morphology. (<b>B</b>) The average cell density (total # of cells per region of interest (ROI); ROI area = 1.23 mm<sup>2</sup>) was calculated using 2–4 ROIs from <span class="html-italic">n</span> = 5 (non-MS), <span class="html-italic">n</span> = 4 (PPMS), <span class="html-italic">n</span> = 6 (RRMS) and <span class="html-italic">n = 6</span> (SPMS) cases. (<b>C</b>) The PAC1 immunoreactivity in cells was determined by normalizing the mean PAC1 staining intensity/average # of cells counted within the same ROIs/cases as in (<b>B</b>). *** <span class="html-italic">p</span> &lt; 0.001 or **** <span class="html-italic">p</span> &lt; 0.0001 vs. non-MS cases, as determined by one-way ANOVA followed by Sidak’s post hoc test. Scale bar = 30 µm. OPC = Oligodendrocyte progenitor cell, PAC1 = Pituitary adenylate cyclase-activating polypeptide type I receptor, MS = multiple sclerosis, NAWM = normal-appearing white matter, RRMS = relapsing–remitting MS, PPMS = primary progressive MS, SPMS = secondary progressive MS.</p> Full article ">Figure 5
<p>PAC1 co-localizes to OLIG2<sup>+</sup> cells in the normal-appearing white matter of RRMS, PPMS and SPMS cases. Representative images showing PAC1 (green)/OLIG2 (red) colocalization in the NAWM of (<b>A</b>) non-MS, (<b>B</b>) RRMS, (<b>C</b>) PPMS or (<b>D</b>) SPMS donors. Nuclei were counterstained with DAPI (blue). Scale bar = 50 µm.</p> Full article ">Figure 6
<p>PAC1 immunoreactivity in representative white matter lesions from selected MS clinical cases. (<b>A</b>–<b>C</b>, left panels) Low-magnification images showing PAC1 immunoreactivity in a lesion taken from one RRMS, PPMS or SPMS-exemplary case. Lesion borders are demarcated by the black dashed lines. Scale bar = 1000 µm. (Insets in <b>A</b>–<b>C</b>) High-power images of ROIs in the left panels (orange and red squares) demonstrating PAC1<sup>+</sup> staining around the lesion edge (top inset) and within the lesion (bottom inset) of the selected RRMS, PPMS and SPMS cases. Scale bar = 30 µm. WM = white matter.</p> Full article ">Figure 7
<p>VPAC1 immunoreactivity in the normal-appearing white matter of RRMS, PPMS and SPMS cases. (<b>A</b>–<b>D</b>) Representative images depicting VPAC1 immunoreactive sites in the NAWM of MS donors with a clinical history of RRMS, PPMS or SPMS and non-MS control cases. Scale bar = 1000 µm. (<b>A′</b>–<b>D′</b>) Insets of the NAWM taken at a higher magnification. Black arrowheads point to VPAC1<sup>+</sup> axonal fibers. Scale bar (NAWM) = 30 µm (<b>B″</b>–<b>D″</b>). Insets showing VPAC1<sup>+</sup> in the grey matter of the selected cases. Black arrowheads indicate VPAC1<sup>+</sup> neurons. Scale bar (GM) = 50 µm. (<b>E</b>) Bar graph showing the average VPAC1 immunoreactivity (IR) in the NAWM. The data shown are the mean grey intensity ± SEM and were calculated by averaging the grey intensity of 2–4 ROIs from <span class="html-italic">n</span> = 5 (non-MS), <span class="html-italic">n</span> = 4 (PPMS), <span class="html-italic">n</span> = 6 (RRMS) and <span class="html-italic">n</span> = 6 (SPMS) cases. Each ROI area = 1.23 mm<sup>2</sup>. No statistical significance was found using one-way ANOVA. Ns = Not significant. VPAC1 = Vasoactive Intestinal Peptide/Pituitary Adenylate Cyclase Activating Polypeptide Receptor 1, MS = multiple sclerosis, NAWM = normal-appearing white matter, WM = white matter, GM = grey matter, RRMS = relapsing–remitting MS, PPMS = primary progressive MS, SPMS = secondary progressive MS.</p> Full article ">Figure 8
<p>VPAC1 immunoreactivity in white matter lesions from selected MS clinical cases. (<b>A</b>–<b>C</b>, left panels) Low-magnification images showing VPAC1 immunoreactivity in a lesion taken from one RRMS, PPMS or SPMS-exemplary case. Lesion borders are demarcated by the black dashed lines. Scale bar = 1000 µm. (Insets in <b>A</b>–<b>C</b>) High-power images of ROIs in left panels (orange and red squares) demonstrating VPAC1<sup>+</sup> staining around the lesion edge (top inset) and within the lesion (bottom inset) of the selected RRMS, PPMS and SPMS cases. Scale bar = 30 µm. WM = white matter.</p> Full article ">Figure 9
<p>VPAC2 immunoreactivity in the normal-appearing white matter of RRMS, PPMS and SPMS cases. (<b>A</b>–<b>D</b>) Representative images depicting VPAC2 immunoreactive (IR) cells in the NAWM of MS donors with a clinical history of RRMS, PPMS or SPMS and non-MS controls. Scale bar = 1000 µm. (<b>A′</b>–<b>D′</b>) Insets of the NAWM taken at a higher magnification. White arrowheads in C′ show VPAC2<sup>+</sup> vessel walls. Scale bar (NAWM) = 30 µm. (<b>B″</b>–<b>D″</b>) Insets showing VPAC2<sup>+</sup> in the grey matter of the selected cases. Black arrowheads indicate VPAC2<sup>+</sup> neurons, whereas white arrowheads show VPAC2-IR in axons. Scale bar (GM) = 50 µm. (<b>E</b>) Bar graph showing the average VPAC1 immunoreactivity (IR) in the NAWM. The data shown are the mean grey intensity ± SEM and were calculated by averaging the grey intensity of 2–4 ROIs from <span class="html-italic">n = 5</span> (non-MS), <span class="html-italic">n</span> = 4 (PPMS), <span class="html-italic">n</span> = 6 (RRMS) and <span class="html-italic">n</span> = 6 (SPMS) cases. Each ROI area = 1.23 mm<sup>2</sup>. **** <span class="html-italic">p</span> &lt; 0.0001 vs. non-MS (control) cases, as determined by one-way ANOVA and Sidak’s post hoc test. VPAC2 = Vasoactive Intestinal Peptide/Pituitary Adenylate Cyclase Activating Polypeptide Receptor 1, MS = multiple sclerosis, NAWM = normal-appearing white matter, GM = grey matter, RRMS = relapsing–remitting MS, PPMS = primary progressive MS, SPMS = secondary progressive MS.</p> Full article ">Figure 10
<p>VPAC2 immunoreactivity in white matter lesions from selected MS clinical cases. (<b>A</b>–<b>C</b>, left panels) Low-magnification images showing VPAC2 immunoreactivity in a lesion taken from one RRMS, PPMS or SPMS-exemplary case. Lesion borders are demarcated by the black dashed lines. Scale bar = 1000 µm. (Insets in <b>A</b>–<b>C</b>) High-power images of ROIs in left panels (orange and red squared) demonstrating VPAC2 staining around the lesion edge (top inset) and within the lesion (bottom inset) of the selected RRMS, PPMS and SPMS cases. Scale bar = 30 µm. GM = grey matter; WM = white matter.</p> Full article ">
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-1
Back to TopTop