The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity

During postnatal development, closure of critical periods coincides with the appearance of extracellular matrix structures, called perineuronal nets (PNN), around various neuronal populations throughout the brain. The absence or presence of PNN strongly correlates with neuronal plasticity. It is not clear how PNN regulate plasticity. The repulsive axon guidance proteins Semaphorin (Sema) 3A and Sema3B are also prominently expressed in the postnatal and adult brain. In the neocortex, Sema3A accumulates in the PNN that form around parvalbumin positive inhibitory interneurons during the closure of critical periods. Sema3A interacts with high-affinity with chondroitin sulfate E, a component of PNN. The localization of Sema3A in PNN and its inhibitory effects on developing neurites are intriguing features and may clarify how PNN mediate structural neural plasticity. In the cerebellum, enhanced neuronal plasticity as a result of an enriched environment correlates with reduced Sema3A expression in PNN. Here, we first review the distribution of Sema3A and Sema3B expression in the rat brain and the biochemical interaction of Sema3A with PNN. Subsequently, we review what is known so far about functional correlates of changes in Sema3A expression in PNN. Finally, we propose a model of how Semaphorins in the PNN may influence local connectivity.

• Publication year

  2016

• Venue

  Journal of Neural Transplantation and Plasticity

• Publication date

  2016-01-14

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/2016/3679545PMID 27057361PMCID 4738953
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Axon guidance proteins in neurological disorders.

  2015cited by this paper
• Retrograde semaphorin signaling regulates synapse elimination in the developing mouse brain

  2014cited by this paper
• Mechanisms of axon regeneration and its inhibition: roles of sulfated glycans.

  2014cited by this paper
• Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells

  2014cited by this paper
• Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling

  2014cited by this paper
• Semaphorins and the dynamic regulation of synapse assembly, refinement, and function.

  2014influential reference
• The Class 4 Semaphorin Sema4D Promotes the Rapid Assembly of GABAergic Synapses in Rodent Hippocampus

  2013cited by this paper
• Sema3A regulates bone-mass accrual through sensory innervations

  2013cited by this paper
• The chemorepulsive axon guidance protein semaphorin3A is a constituent of perineuronal nets in the adult rodent brain.

  2013cited by this paper
• Semaphorin 3A Binds to the Perineuronal Nets via Chondroitin Sulfate Type E Motifs in Rodent Brains*

  2013cited by this paper
• Toward libraries of biotinylated chondroitin sulfate analogues: from synthesis to in vivo studies.

  2013influential reference
• Choroid-plexus-derived Otx2 homeoprotein constrains adult cortical plasticity.

  2013cited by this paper
• The role of semaphorins and their receptors in vascular development and cancer.

  2013cited by this paper
• Modulation of semaphorin3A in perineuronal nets during structural plasticity in the adult cerebellum.

  2013influential reference
• Sema4D localizes to synapses and regulates GABAergic synapse development as a membrane-bound molecule in the mammalian hippocampus.

  2013cited by this paper
• Arylsulfatase B Improves Locomotor Function after Mouse Spinal Cord Injury

  2013influential reference
• Semaphorin Signaling in Vertebrate Neural Circuit Assembly

  2012cited by this paper
• NgR1 and NgR3 are Receptors for Chondroitin Sulfate Proteoglycans

  2012cited by this paper
• Otx2 Binding to Perineuronal Nets Persistently Regulates Plasticity in the Mature Visual Cortex

  2012influential reference
• Neuropilins lock secreted semaphorins onto plexins in a ternary signaling complex

  2012cited by this paper
• Persistent cortical plasticity by upregulation of chondroitin 6-sulfation

  2012cited by this paper
• Collapsin Response Mediator Proteins Regulate Neuronal Development and Plasticity by Switching Their Phosphorylation Status

  2012cited by this paper
• Receptor complexes for each of the Class 3 Semaphorins

  2012cited by this paper
• The perineuronal net and the control of CNS plasticity

  2012cited by this paper
• Plexin structures are coming: opportunities for multilevel investigations of semaphorin guidance receptors, their cell signaling mechanisms, and functions

  2012cited by this paper
• Leukocyte Common Antigen-Related Phosphatase Is a Functional Receptor for Chondroitin Sulfate Proteoglycan Axon Growth Inhibitors

  2011cited by this paper
• Semaphorin 3E–Plexin-D1 signaling controls pathway-specific synapse formation in the striatum

  2011cited by this paper
• 6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

  2011cited by this paper
• Experience-Dependent Plasticity and Modulation of Growth Regulatory Molecules at Central Synapses

  2011cited by this paper
• Chondroitinase Combined with Rehabilitation Promotes Recovery of Forelimb Function in Rats with Chronic Spinal Cord Injury

  2011cited by this paper
• Time Course of Gene Expression Profiling in the Liver of Experimental Mice Infected with Echinococcus multilocularis

  2011cited by this paper
• Extracellular matrix and perineuronal nets in CNS repair

  2011cited by this paper
• Proteomic analysis of potential keratan sulfate, chondroitin sulfate A, and hyaluronic acid molecular interactions.

  2010cited by this paper
• Mical links semaphorins to F-actin disassembly

  2010cited by this paper
• Immunohistochemical Distribution of PlexinA4 in the Adult Rat Central Nervous System

  2010cited by this paper
• Flotillin-Mediated Endocytic Events Dictate Cell Type-Specific Responses to Semaphorin 3A

  2010cited by this paper
• Animals lacking link protein have attenuated perineuronal nets and persistent plasticity.

  2010cited by this paper
• Guidance molecules in synapse formation and plasticity.

  2010cited by this paper
• Structural basis of semaphorin–plexin signalling

  2010cited by this paper
• Chondroitin sulfate acts in concert with semaphorin 3A to guide tangential migration of cortical interneurons in the ventral telencephalon.

  2010cited by this paper
• Aggrecan-based extracellular matrix shows unique cortical features and conserved subcortical principles of mammalian brain organization in the Madagascan lesser hedgehog tenrec (Echinops telfairi Martin, 1838).

  2010cited by this paper
• Converting juvenile into adult plasticity: a role for the brain’s extracellular matrix

  2010cited by this paper
• Secreted Semaphorins Control Spine Distribution and Morphogenesis in the Postnatal CNS

  2009cited by this paper
• Matrix-Dependent Local Retention of Secretory Vesicle Cargo in Cortical Neurons

  2009cited by this paper
• Semaphorin 5B mediates synapse elimination in hippocampal neurons

  2009cited by this paper
• Semaphorin function in neural plasticity and disease.

  2009cited by this paper
• The many faces of semaphorins: from development to pathology

  2009cited by this paper
• PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

  2009cited by this paper
• Specificity of sensory–motor connections encoded by Sema3e–Plxnd1 recognition

  2009cited by this paper
• Overexpression of GAP‐43 modifies the distribution of the receptors for myelin‐associated growth‐inhibitory proteins in injured Purkinje axons

  2009cited by this paper
• Release of MICAL Autoinhibition by Semaphorin-Plexin Signaling Promotes Interaction with Collapsin Response Mediator Protein

  2008cited by this paper
• Chondroitin-4-sulfation negatively regulates axonal guidance and growth

  2008cited by this paper
• Distribution and synthesis of extracellular matrix proteoglycans, hyaluronan, link proteins and tenascin‐R in the rat spinal cord

  2008cited by this paper
• Experience-dependent transfer of Otx2 homeoprotein into the visual cortex activates postnatal plasticity.

  2008cited by this paper
• Chondroitin/dermatan sulfate in the central nervous system.

  2007cited by this paper
• Semaphorin and neuropilin co-expression in motoneurons sets axon sensitivity to environmental semaphorin sources during motor axon pathfinding

  2007cited by this paper
• The CRMP family of proteins and their role in Sema3A signaling.

  2007cited by this paper
• Upregulation of aggrecan, link protein 1, and hyaluronan synthases during formation of perineuronal nets in the rat cerebellum

  2007cited by this paper
• Semaphorin regulation of cellular morphology.

  2007cited by this paper
• GTPases in semaphorin signaling.

  2007cited by this paper
• Regulation of Spine Development by Semaphorin3A through Cyclin-Dependent Kinase 5 Phosphorylation of Collapsin Response Mediator Protein 1

  2007cited by this paper
• Effect of binocular retinal lesions on CRMP2 and CRMP4 but not Dyn I and Syt I expression in adult cat area 17

  2007cited by this paper
• An RNAi-based approach identifies molecules required for glutamatergic and GABAergic synapse development.

  2007cited by this paper
• Age-dependent alterations in CRMP2 and CRMP4 protein expression profiles in cat visual cortex.

  2006cited by this paper
• Composition of Perineuronal Net Extracellular Matrix in Rat Brain

  2006cited by this paper
• A selective Sema3A inhibitor enhances regenerative responses and functional recovery of the injured spinal cord

  2006cited by this paper
• Chondroitinase ABC Promotes Sprouting of Intact and Injured Spinal Systems after Spinal Cord Injury

  2006cited by this paper
• Regulation of Dendritic Branching and Spine Maturation by Semaphorin3A-Fyn Signaling

  2006cited by this paper
• Genetic Manipulation of Intraspinal Plasticity after Spinal Cord Injury Alters the Severity of Autonomic Dysreflexia

  2006cited by this paper
• Composition of perineuronal nets in the adult rat cerebellum and the cellular origin of their components

  2006cited by this paper
• Vesicular Trafficking of Semaphorin 3A is Activity‐Dependent and Differs Between Axons and Dendrites

  2006cited by this paper
• Distribution of pyramidal cells associated with perineuronal nets in the neocortex of rat.

  2006cited by this paper
• Semaphorin3A regulates synaptic function of differentiated hippocampal neurons

  2006cited by this paper
• Enriched environments, experience-dependent plasticity and disorders of the nervous system

  2006cited by this paper
• Critical period plasticity in local cortical circuits

  2005cited by this paper
• Semaphorins command cells to move

  2005cited by this paper
• Secreted Semaphorins Modulate Synaptic Transmission in the Adult Hippocampus

  2005cited by this paper
• Semaphorin 3A displays a punctate distribution on the surface of neuronal cells and interacts with proteoglycans in the extracellular matrix.

  2005cited by this paper
• Functions of heparan sulfate proteoglycans in cell signaling during development

  2004cited by this paper
• Netrin-1 and Semaphorin 3A Promote or Inhibit Cortical Axon Branching, Respectively, by Reorganization of the Cytoskeleton

  2004cited by this paper
• Critical period regulation.

  2004cited by this paper
• GAP‐43 overexpression in adult mouse Purkinje cells overrides myelin‐derived inhibition of neurite growth

  2004cited by this paper
• Structural bases for CRMP function in plexin‐dependent semaphorin3A signaling

  2004cited by this paper
• Semaphorin 5A is a bifunctional axon guidance cue regulated by heparan and chondroitin sulfate proteoglycans.

  2004cited by this paper
• Temporal specific patterns of semaphorin gene expression in rat brain after kainic acid‐induced status epilepticus

  2003cited by this paper
• Transient downregulation of Sema3A mRNA in a rat model for temporal lobe epilepsy. A novel molecular event potentially contributing to mossy fiber sprouting.

  2003cited by this paper
• Injury-induced class 3 semaphorin expression in the rat spinal cord.

  2002cited by this paper
• MICALs, a family of conserved flavoprotein oxidoreductases, function in plexin-mediated axonal repulsion.

  2002cited by this paper
• Reactivation of Ocular Dominance Plasticity in the Adult Visual Cortex

  2002cited by this paper
• Regeneration of CNS axons back to their target following treatment of adult rat brain with chondroitinase ABC

  2001cited by this paper
• Neural consequences of enviromental enrichment

  2000cited by this paper
• Plexin-neuropilin-1 complexes form functional semaphorin-3A receptors.

  1999cited by this paper
• Expression of the gene encoding the chemorepellent semaphorin III is induced in the fibroblast component of neural scar tissue formed following injuries of adult but not neonatal CNS.

  1999cited by this paper
• Unified nomenclature for the semaphorins/collapsins [1]

  1999cited by this paper
• Unified nomenclature for the semaphorins/collapsins. Semaphorin Nomenclature Committee.

  1999cited by this paper
• Anatomical distribution of the chemorepellent semaphorin III/collapsin‐1 in the adult rat and human brain: Predominant expression in structures of the olfactory‐hippocampal pathway and the motor system

  1998cited by this paper
• Patterning of cortical efferent projections by semaphorin-neuropilin interactions.

  1998cited by this paper
• Semaphorins act as attractive and repulsive guidance signals during the development of cortical projections.

  1998cited by this paper
• Neuropilin-2, a novel member of the neuropilin family, is a high affinity receptor for the semaphorins Sema E and Sema IV but not Sema III.

  1997cited by this paper
• Neuropilin is a semaphorin III receptor.

  1997cited by this paper

• Semaphorin 3A-mediated perineuronal nets formation incubates depressive-like behaviors in male mice via activating parvalbumin-expressing interneurons

  2025cites this paper
• Nonneuronal contributions to synaptic function.

  2025cites this paper
• Glycosaminoglycan sugar side chains on perineuronal nets in the fastigial nucleus regulate motor skills

  2025cites this paper
• The Role of Perineuronal Nets in Physiology and Disease: Insights from Recent Studies

  2025cites this paper
• Bisphenol S interrupted axonogenesis on a human embryonic stem cells derived neural differentiation model: Conserved axon guidance and WNT signaling pathway involved.

  2025cites this paper
• Semaphorin7A patterns neural circuitry in the lateral line of the zebrafish

  2024cites this paper
• FMRP regulation of aggrecan mRNA translation controls perineuronal net development

  2024cites this paper
• The mechanisms of perineuronal net abnormalities in contributing aging and neurological diseases.

  2023cites this paper
• Dynamic regulation of the extracellular matrix in reward memory processes: a question of time

  2023cites this paper
• The role of Wnt, ARL4C, and Sema3A in developmental process and disease pathogenesis

  2023cites this paper
• Neuroplastic Changes in Addiction Memory—How Music Therapy and Music-Based Intervention May Reduce Craving: A Narrative Review

  2023cites this paper
• 4-methylumbelliferone enhances neuroplasticity in the central nervous system: potential oral treatment for SCI

  2023cites this paper
• CDKL5 deficiency results in atypical subregion-specific expression of perineuronal nets during mouse visual critical period

  2023cites this paper
• Perineuronal nets: Cruise from a honeycomb to the safety nets.

  2022cites this paper
• An increase in Semaphorin 3A biases the axonal direction and induces an aberrant dendritic arborization in an in vitro model of human neural progenitor differentiation

  2022cites this paper
• The role of enriched environment in neural development and repair

  2022cites this paper
• Net gain and loss: influence of natural rewards and drugs of abuse on perineuronal nets

  2022cites this paper
• Wild-type MECP2 expression coincides with age-dependent sensory phenotypes in a female mouse model for Rett syndrome

  2022cites this paper
• Non-Cell-Autonomous Factors Implicated in Parvalbumin Interneuron Maturation and Critical Periods

  2022cites this paper
• Semaphorin7A patterns neural circuitry 1 in the lateral line of the zebrafish 2

  2022cites this paper
• Perineuronal Nets and Metal Cation Concentrations in the Microenvironments of Fast-Spiking, Parvalbumin-Expressing GABAergic Interneurons: Relevance to Neurodevelopment and Neurodevelopmental Disorders

  2021cites this paper
• Cerebral Modifications in Glaucoma and Macular Degeneration: Analysis of Current Evidence in Literature and Their Implications on Therapeutic Perspectives

  2021cites this paper
• Modelling and Refining Neuronal Circuits with Guidance Cues: Involvement of Semaphorins

  2021cites this paper
• The CNS/PNS Extracellular Matrix Provides Instructive Guidance Cues to Neural Cells and Neuroregulatory Proteins in Neural Development and Repair

  2021cites this paper
• Semaphorins in Adult Nervous System Plasticity and Disease

  2021cites this paper
• Sexually dimorphic perineuronal nets in the rodent and primate reproductive circuit

  2021cites this paper
• Fibrosis in the central nervous system: from the meninges to the vasculature

  2021cites this paper
• Ankyrin-R regulates fast-spiking interneuron excitability through perineuronal nets and Kv3.1b K+ channels

  2021cites this paper
• Quantitative Proteomics Reveals Significant Differences between Mouse Brain Formations in Expression of Proteins Involved in Neuronal Plasticity during Aging

  2021cites this paper
• It Takes Two to Tango: Secondary Entry Pathway for SARS-CoV-2 Induces Analgesia

  2021cites this paper
• Surfactant protein C is associated with perineuronal nets and shows age-dependent changes of brain content and hippocampal deposits in wildtype and 3xTg mice.

  2021cites this paper
• Semaphorin 3A—Glycosaminoglycans Interaction as Therapeutic Target for Axonal Regeneration

  2021influential citation
• Decreased Presence of Mast Cells in the Bursa Premacularis of Proliferative Diabetic Retinopathy

  2021cites this paper
• EB_A_307551 159..173

  2021cites this paper
• EA Improves the Motor Function in Rats with Spinal Cord Injury by Inhibiting Signal Transduction of Semaphorin3A and Upregulating of the Peripheral Nerve Networks

  2020cites this paper
• Incubation of depression: ECM assembly and parvalbumin interneurons after stress.

  2020cites this paper
• Cerebral Modifications and Visual Pathway Reorganization in Maculopathy: A Systematic Review

  2020cites this paper
• EHMT1 regulates Parvalbumin-positive interneuron development and GABAergic input in sensory cortical areas

  2020cites this paper
• BDNF and JNK Signaling Modulate Cortical Interneuron and Perineuronal Net Development: Implications for Schizophrenia-Linked 16p11.2 Duplication Syndrome

  2020cites this paper
• Molecular signature of extracellular matrix pathology in schizophrenia

  2020cites this paper
• The Responsiveness of Thymic Stromal Cells to semaphorin-3A

  2020cites this paper
• Histochemical Characterization of the Vestibular Y-Group in Monkey

  2020cites this paper
• Extracellular Matrix in Neural Plasticity and Regeneration

  2020cites this paper
• Reconsideration of the Semaphorin-3A Binding Motif Found in Chondroitin Sulfate Using Galnac4s-6st-Knockout Mice

  2020cites this paper
• Hypothalamic Regulation of Glucose Homeostasis: Is the Answer in the Matrix?

  2020cites this paper
• Title: Disruption of rat deep cerebellar perineuronal net alters eyeblink conditioning and neuronal electrophysiology.

  2020cites this paper
• Inhibition of Semaphorin3A Promotes Ocular Dominance Plasticity in the Adult Rat Visual Cortex

  2019cites this paper
• Perineuronal nets in brain physiology and disease.

  2019cites this paper
• The roles of perineuronal nets and the perinodal extracellular matrix in neuronal function

  2019cites this paper
• Lateralized Expression of Cortical Perineuronal Nets during Maternal Experience is Dependent on MECP2

  2019cites this paper
• Neuronal Pentraxin 2 Binds PNNs and Enhances PNN Formation

  2019cites this paper
• Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation

  2019cites this paper
• Dynamic perineuronal net expression during learned maternal behavior is cortical hemisphere-specific and dependent on methyl-CpG-binding protein 2

  2019cites this paper
• Structural Variation of Chondroitin Sulfate Chains Contributes to the Molecular Heterogeneity of Perineuronal Nets

  2018cites this paper
• Perineuronal Net Formation during the Critical Period for Neuronal Maturation in the Hypothalamic Arcuate Nucleus

  2018cites this paper
• Hapln4/Bral2 is a selective regulator for formation and transmission of GABAergic synapses between Purkinje and deep cerebellar nuclei neurons

  2018cites this paper
• Concepts toward directing human astroplasticity to promote neuroregeneration

  2018cites this paper
• A rationally designed NRP1-independent superagonist SEMA3A mutant is an effective anticancer agent

  2018cites this paper
• Perineuronal Net Formation and the Critical Period for Neuronal Maturation in the

  2018cites this paper
• Characterisation of semaphorin 3A-chondroitin sulphate interaction in the central nervous system

  2018cites this paper
• A Sweet Talk: The Molecular Systems of Perineuronal Nets in Controlling Neuronal Communication

  2017cites this paper
• Characterization of Spontaneous Motor Recovery and Changes in Plasticity-Limiting Perineuronal Nets Following Cortical and Subcortical Stroke

  2017cites this paper
• Levels of Perineuronal Nets in the Basolateral Amygdala Are Correlated with Sex Differences in Fear Learning

  2017cites this paper
• Synaptic changes upon removal of extracellular perineuronal nets in adult mouse visual cortex

  2017cites this paper
• Investigating chondroitin sulphate proteoglycans as a therapeutic target for Parkinson's disease

  2017cites this paper
• A recognizable type of syndromic short stature with arthrogryposis caused by bi‐allelic SEMA3A loss‐of‐function variants

  2017cites this paper
• Sugarcoated Perineuronal Nets Regulate “GABAergic” Transmission: Bittersweet Hypothesis in Autism Spectrum Disorder

  2017cites this paper
• Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine‐induced conditioned place preference and self‐administration

  2017cites this paper
• Antibody recognizing 4-sulfated chondroitin sulfate proteoglycans restores memory in tauopathy-induced neurodegeneration.

  2017cites this paper
• Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan.

  2017cites this paper
• Shear-Induced Amyloid Formation in the Brain: II. An Experimental System for Monitoring Amyloid Shear Processes and Investigating Potential Spinal Tap Problems

  2017cites this paper
• Multiple roles for the extracelllular matrix protein Tenascin-X in nerve gut function

  2016cites this paper
• Casting a Wide Net: Role of Perineuronal Nets in Neural Plasticity

  2016cites this paper
• Contrôler la plasticité du cortex cérébral adulte à travers l'action non-autonome de l'homéoprotéine Otx2

  2015cites this paper