5
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects of PACAP on Schwann Cells: Focus on Nerve Injury

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal regrowth and restoration of myelin sheaths on regenerating axons. Following nerve injury, Schwann cells respond adaptively to damage by acquiring a new phenotype. In particular, some of them localize in the distal stump to form the Bungner band, a regeneration track in the distal site of the injured nerve, whereas others produce cytokines involved in recruitment of macrophages infiltrating into the nerve damaged area for axonal and myelin debris clearance. Several neurotrophic factors, including pituitary adenylyl cyclase-activating peptide (PACAP), promote survival and axonal elongation of injured neurons. The present review summarizes the evidence existing in the literature demonstrating the autocrine and/or paracrine action exerted by PACAP to promote remyelination and ameliorate the peripheral nerve inflammatory response following nerve injury.

          Related collections

          Most cited references100

          • Record: found
          • Abstract: found
          • Article: found
          Is Open Access

          The repair Schwann cell and its function in regenerating nerves

          Abstract Nerve injury triggers the conversion of myelin and non‐myelin (Remak) Schwann cells to a cell phenotype specialized to promote repair. Distal to damage, these repair Schwann cells provide the necessary signals and spatial cues for the survival of injured neurons, axonal regeneration and target reinnervation. The conversion to repair Schwann cells involves de‐differentiation together with alternative differentiation, or activation, a combination that is typical of cell type conversions often referred to as (direct or lineage) reprogramming. Thus, injury‐induced Schwann cell reprogramming involves down‐regulation of myelin genes combined with activation of a set of repair‐supportive features, including up‐regulation of trophic factors, elevation of cytokines as part of the innate immune response, myelin clearance by activation of myelin autophagy in Schwann cells and macrophage recruitment, and the formation of regeneration tracks, Bungner's bands, for directing axons to their targets. This repair programme is controlled transcriptionally by mechanisms involving the transcription factor c‐Jun, which is rapidly up‐regulated in Schwann cells after injury. In the absence of c‐Jun, damage results in the formation of a dysfunctional repair cell, neuronal death and failure of functional recovery. c‐Jun, although not required for Schwann cell development, is therefore central to the reprogramming of myelin and non‐myelin (Remak) Schwann cells to repair cells after injury. In future, the signalling that specifies this cell requires further analysis so that pharmacological tools that boost and maintain the repair Schwann cell phenotype can be developed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Isolation of a novel 38 residue-hypothalamic polypeptide which stimulates adenylate cyclase in pituitary cells.

            A novel neuropeptide which stimulates adenylate cyclase in rat anterior pituitary cell cultures was isolated from ovine hypothalamic tissues. Its amino acid sequence was revealed as: His-Ser-Asp-Gly-Ile-Phe-Thr-Asp-Ser-Tyr-Ser-Arg-Tyr-Arg-Lys-Gln- Met-Ala- Val-Lys-Lys-Tyr-Leu-Ala-Ala-Val-Leu-Gly-Lys-Arg-Tyr-Lys-Gln-Arg-Val-Lys-Asn-Lys - NH2. The N-terminal sequence shows 68% homology with vasoactive intestinal polypeptide (VIP) but its adenylate cyclase stimulating activity was at least 1000 times greater than that of VIP. It increased release of growth hormone (GH), prolactin (PRL), corticotropin (ACTH) and luteinizing hormone (LH) from superfused rat pituitary cells at as small a dose as 10(-10)M (GH, PRL, ACTH) or 10(-9)M (LH). Whether these hypophysiotropic effects are the primary actions of the peptide or what physiological action in the pituitary is linked with the stimulation of adenylate cyclase by this peptide remains to be determined.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              The Success and Failure of the Schwann Cell Response to Nerve Injury

              The remarkable plasticity of Schwann cells allows them to adopt the Remak (non-myelin) and myelin phenotypes, which are specialized to meet the needs of small and large diameter axons, and differ markedly from each other. It also enables Schwann cells initially to mount a strikingly adaptive response to nerve injury and to promote regeneration by converting to a repair-promoting phenotype. These repair cells activate a sequence of supportive functions that engineer myelin clearance, prevent neuronal death, and help axon growth and guidance. Eventually, this response runs out of steam, however, because in the long run the phenotype of repair cells is unstable and their survival is compromised. The re-programming of Remak and myelin cells to repair cells, together with the injury-induced switch of peripheral neurons to a growth mode, gives peripheral nerves their strong regenerative potential. But it remains a challenge to harness this potential and devise effective treatments that maintain the initial repair capacity of peripheral nerves for the extended periods typically required for nerve repair in humans.
                Bookmark

                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                03 November 2020
                November 2020
                : 21
                : 21
                : 8233
                Affiliations
                [1 ]Department of Biomedical and Biotechnological Sciences, Section of Anatomy, Histology and Movement Sciences, University of Catania, 95100 Catania, Italy; graziamaugeri@ 123456unict.it (G.M.); g.musumeci@ 123456unict.it (G.M.)
                [2 ]Department of Drug Sciences, University of Catania, 95100 Catania, Italy; agata.damico@ 123456unict.it
                [3 ]Department of Anatomy, MTA-PTE PACAP Research Team, University of Pécs Medical School, Szigeti út 12, H-7624 Pécs, Hungary; dora.reglodi@ 123456aok.pte.hu
                Author notes
                [* ]Correspondence: vdagata@ 123456unict.it ; Tel.: +39-095-3782039
                [†]

                These authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-8260-8890
                https://orcid.org/0000-0003-1114-8265
                Article
                ijms-21-08233
                10.3390/ijms21218233
                7663204
                33153152
                c896e00e-7e7d-4097-ad49-cf3c3b5c2306
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 September 2020
                : 02 November 2020
                Categories
                Review

                Molecular biology
                peripheral nervous system,schwann cells,pacap,neuroprotection,regeneration
                Molecular biology
                peripheral nervous system, schwann cells, pacap, neuroprotection, regeneration

                Comments

                Comment on this article