Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation

Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We...

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Main Authors: Byeong Gwan Song, Su Yeon Kwon, Jae Won Kyung, Eun Ji Roh, Hyemin Choi, Chang Su Lim, Seong Bae An, Seil Sohn, Inbo Han
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/11/6218
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author Byeong Gwan Song
Su Yeon Kwon
Jae Won Kyung
Eun Ji Roh
Hyemin Choi
Chang Su Lim
Seong Bae An
Seil Sohn
Inbo Han
author_facet Byeong Gwan Song
Su Yeon Kwon
Jae Won Kyung
Eun Ji Roh
Hyemin Choi
Chang Su Lim
Seong Bae An
Seil Sohn
Inbo Han
author_sort Byeong Gwan Song
collection DOAJ
description Synaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.
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spelling doaj.art-94e35ceecb434bfda8c4fdf1b0526fb72023-11-23T14:11:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012311621810.3390/ijms23116218Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar FormationByeong Gwan Song0Su Yeon Kwon1Jae Won Kyung2Eun Ji Roh3Hyemin Choi4Chang Su Lim5Seong Bae An6Seil Sohn7Inbo Han8Department of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaDepartment of Neurosurgery, CHA University School of Medicine, CHA Bundang Medical Center, Seongnam-si 13496, Gyeonggi-do, KoreaSynaptic cell adhesion molecules (SynCAMs) play an important role in the formation and maintenance of synapses and the regulation of synaptic plasticity. SynCAM3 is expressed in the synaptic cleft of the central nervous system (CNS) and is involved in the connection between axons and astrocytes. We hypothesized that SynCAM3 may be related to the astrocytic scar (glial scar, the most important factor of CNS injury treatment) through extracellular matrix (ECM) reconstitution. Thus, we investigated the influence of the selective removal of SynCAM3 on the outcomes of spinal cord injury (SCI). SynCAM3 knock-out (KO) mice were subjected to moderate compression injury of the lower thoracic spinal cord using wild-type (WT) (C57BL/6JJc1) mice as controls. Single-cell RNA sequencing analysis over time, quantitative real-time polymerase chain reaction (qRT-PCR) analysis, and immunohistochemistry (IHC) showed reduced scar formation in SynCAM3 KO mice compared to WT mice. SynCAM3 KO mice showed improved functional recovery from SCI by preventing the transformation of reactive astrocytes into scar-forming astrocytes, resulting in improved ECM reconstitution at four weeks after injury. Our findings suggest that SynCAM3 could be a novel therapeutic target for SCI.https://www.mdpi.com/1422-0067/23/11/6218spinal cord injurycell adhesion moleculessynaptic adhesion moleculesastrocyteglial scarextracellular matrix
spellingShingle Byeong Gwan Song
Su Yeon Kwon
Jae Won Kyung
Eun Ji Roh
Hyemin Choi
Chang Su Lim
Seong Bae An
Seil Sohn
Inbo Han
Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
International Journal of Molecular Sciences
spinal cord injury
cell adhesion molecules
synaptic adhesion molecules
astrocyte
glial scar
extracellular matrix
title Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
title_full Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
title_fullStr Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
title_full_unstemmed Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
title_short Synaptic Cell Adhesion Molecule 3 (SynCAM3) Deletion Promotes Recovery from Spinal Cord Injury by Limiting Glial Scar Formation
title_sort synaptic cell adhesion molecule 3 syncam3 deletion promotes recovery from spinal cord injury by limiting glial scar formation
topic spinal cord injury
cell adhesion molecules
synaptic adhesion molecules
astrocyte
glial scar
extracellular matrix
url https://www.mdpi.com/1422-0067/23/11/6218
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