ab43e360517f524fd147b0c98f6b8dfa cells_a2022v11n7p1083.pdf 8b2af8ff6fa420c4fe0be9468d0491bde7841da8 cells_a2022v11n7p1083.pdf b424ce2e73b38c15ac56879193d53247f9fea10d669f395da9272bf16da5f150 cells_a2022v11n7p1083.pdf Title: Effects of Sigma-1 Receptor Ligands on Peripheral Nerve Regeneration Subject: Peripheral nerve injuries lead to the loss of motor, sensory and autonomic functions in the territories supplied by the injured nerve. Currently, nerve injuries are managed by surgical repair procedures, and there are no effective drugs in the clinic for improving the capacity of axonal regeneration. Sigma-1 receptor (Sig-1R) is an endoplasmic reticulum chaperon protein involved in many functions, including neuroprotection and neuroplasticity. A few previous studies using Sig-1R ligands reported results that suggest this receptor as a putative target to enhance regeneration. The aim of this study was to evaluate the possible effects of Sig-1R ligands on axonal regeneration in a sciatic nerve section and repair model in mice. To this end, mice were treated either with the Sig-1R agonist PRE-084 or the antagonist BD1063, and a Sig-1R knock-out (KO) mice group was also studied. The electrophysiological and histological data showed that treatment with Sig-1R ligands, or the lack of this protein, did not markedly modify the process of axonal regeneration and target reinnervation after sciatic nerve injury. Nevertheless, the nociceptive tests provided results indicating a role of Sig-1R in sensory perception after nerve injury, and immunohistochemical labeling indicated a regulatory role in inflammatory cell infiltration in the injured nerve. Keywords: peripheral nerve injury; sigma-1 receptor; PRE-084; BD1063; Sig-1R KO; electrophysiology; nociception; intra-epidermal nerve fibers; myelinated axons regeneration; macrophage Author: Patrick Cottilli, Núria Gaja-Capdevila and Xavier Navarro Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 25 02:34:35 2022 CET ModDate: Fri Mar 25 02:38:44 2022 CET Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 14 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 4706939 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- ENLEMO+VnURWPalladioL-Bold Type 1 Custom yes yes no 10 0 CIQLLF+VnURWPalladioL Type 1 Custom yes yes no 15 0 OQRBFP+URWPalladioL-Bold Type 1 Custom yes yes no 19 0 PUHJMK+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 XXGNXV+URWPalladioL-Ital Type 1 Custom yes yes no 28 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 36 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 40 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 44 0 PFKOHU+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 56 0 QMDDXF+CMSY10 Type 1 Builtin yes yes no 78 0 GIIJWT+EURM10 Type 1 Builtin yes yes no 91 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2023-05-31 02:31:48 CEST RepresentationInformation: cells_a2022v11n7p1083.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2022-03-28 11:11:27 CEST Size: 4706939 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 318 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@44c8afef Item: Title: Materials and Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7b69c6ba Children: Item: Title: Animals and Surgical Procedures Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@46daef40 Item: Title: Walking Track Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@12f41634 Item: Title: Electrophysiological Tests Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Pinprick Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Item: Title: Pincher Test Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Immunohistochemical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Histological Assessment of Regenerated Myelinated Axons Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Statistical Analyses Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Children: Item: Title: Functional Motor Recovery Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Electrophysiological Results of Nerve Regeneration after Sciatic Nerve Section and Repair Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Item: Title: Treatment with Sig-1R Antagonist BD1063 Produces Hyposensitivity after Nerve Injury Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Skin Reinnervation and Number of Regenerated Axons after Nerve Injury Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: BD1063 Treatment Reduces Infiltrating Macrophages in the Injured Nerve Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Info: Title: Effects of Sigma-1 Receptor Ligands on Peripheral Nerve Regeneration Author: Patrick Cottilli, Núria Gaja-Capdevila and Xavier Navarro Subject: Peripheral nerve injuries lead to the loss of motor, sensory and autonomic functions in the territories supplied by the injured nerve. Currently, nerve injuries are managed by surgical repair procedures, and there are no effective drugs in the clinic for improving the capacity of axonal regeneration. Sigma-1 receptor (Sig-1R) is an endoplasmic reticulum chaperon protein involved in many functions, including neuroprotection and neuroplasticity. A few previous studies using Sig-1R ligands reported results that suggest this receptor as a putative target to enhance regeneration. The aim of this study was to evaluate the possible effects of Sig-1R ligands on axonal regeneration in a sciatic nerve section and repair model in mice. To this end, mice were treated either with the Sig-1R agonist PRE-084 or the antagonist BD1063, and a Sig-1R knock-out (KO) mice group was also studied. The electrophysiological and histological data showed that treatment with Sig-1R ligands, or the lack of this protein, did not markedly modify the process of axonal regeneration and target reinnervation after sciatic nerve injury. Nevertheless, the nociceptive tests provided results indicating a role of Sig-1R in sensory perception after nerve injury, and immunohistochemical labeling indicated a regulatory role in inflammatory cell infiltration in the injured nerve. Keywords: peripheral nerve injury; sigma-1 receptor; PRE-084; BD1063; Sig-1R KO; electrophysiology; nociception; intra-epidermal nerve fibers; myelinated axons regeneration; macrophage Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Fri Mar 25 02:34:35 CET 2022 ModDate: Fri Mar 25 02:38:44 CET 2022 ID: 0xccc6e3cdf32183ab6c5ae2fb32944d23, 0xccc6e3cdf32183ab6c5ae2fb32944d23 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: OQRBFP+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 134 FontDescriptor: FontName: OQRBFP+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: PUHJMK+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 252 FontDescriptor: FontName: PUHJMK+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: ENLEMO+VnURWPalladioL-Bold FontSubset: true FirstChar: 243 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