Extracellular matrix and perineuronal nets in CNS repair

Perineuronal nets (PNs) in the brains of tenascin-R-deficient ( tn-r −/− ) mice develop in temporal concordance with those of wild-type ( tn-r +/+ ) mice. However, the histological appearance of PNs is abnormal in adult tn-r −/− mice. Here, we investigated whether similar defects are also seen in dissociated and organotypic cultures from hippocampus and forebrain of tn-r −/− mice and whether the structure of PNs could be normalized. In tn-r −/− cultures, accumulations of several extracellular matrix molecules were mostly associated with somata, whereas dendrites were sparsely covered, compared with tn-r +/+ mice. Experiments to normalize the structure of PNs in tn-r −/− organotypic slice cultures by depolarization of neurons, or by co-culturing tn-r +/+ and tn-r −/− brain slices failed to restore a normal PN phenotype. However, formation of dendritic PNs in cultures was improved by the application of tenascin-R protein and rescued by polyclonal antibodies to aggrecan and a bivalent, but not monovalent form of the lectin Wisteria floribunda agglutinin. These results show that tenascin-R and aggrecan are decisive contributors to formation and stabilization of PNs and that tenascin-R may implement these functions by clustering of aggrecan. Proposed approaches for restoration of normal PN structure are noteworthy in the context of PN abnormalities in neurological disorders, such as epilepsy, schizophrenia and addiction.

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Caught in the Net: Perineuronal Nets and Addiction

Neural Plasticity ◽

10.1155/2016/7538208 ◽

2016 ◽

Vol 2016 ◽

pp. 1-8 ◽

Cited By ~ 16

Author(s):

Megan Slaker ◽

Jordan M. Blacktop ◽

Barbara A. Sorg

Keyword(s):

Extracellular Matrix ◽

Drugs Of Abuse ◽

Perineuronal Nets ◽

Drug Induced ◽

Brain Circuitry ◽

Induced Changes ◽

The Brain

Exposure to drugs of abuse induces plasticity in the brain and creates persistent drug-related memories. These changes in plasticity and persistent drug memories are believed to produce aberrant motivation and reinforcement contributing to addiction. Most studies have explored the effect drugs of abuse have on pre- and postsynaptic cells and astrocytes; however, more recently, attention has shifted to explore the effect these drugs have on the extracellular matrix (ECM). Within the ECM are unique structures arranged in a net-like manner, surrounding a subset of neurons called perineuronal nets (PNNs). This review focuses on drug-induced changes in PNNs, the molecules that regulate PNNs, and the expression of PNNs within brain circuitry mediating motivation, reward, and reinforcement as it pertains to addiction.

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Perineuronal Nets in the Superior Olivary Complex

The Oxford Handbook of the Auditory Brainstem ◽

10.1093/oxfordhb/9780190849061.013.12 ◽

2018 ◽

pp. 420-444 ◽

Cited By ~ 1

Author(s):

Markus Morawski ◽

Mandy Sonntag

Keyword(s):

Experimental Data ◽

Extracellular Matrix ◽

Synaptic Plasticity ◽

Neuronal Excitability ◽

Auditory Brainstem ◽

Specific Form ◽

Superior Olivary Complex ◽

Perineuronal Nets ◽

Neuronal Somata ◽

Main Components

This chapter addresses perineuronal nets in the superior olivary complex, a collection of nuclei in the auditory brainstem that are involved in the processing of sound source location. Perineuronal nets, a specific form of extracellular matrix, are believed to control synaptic plasticity. They surround neuronal somata and dendrites of specific types of neurons, among which are many neurons of the superior olivary complex. The chapter describes the distribution of perineuronal nets in the superior olivary complex, focusing on controversial results and discussing underlying reasons. In addition, it considers the development of perineuronal nets and highlights differences between the main components of perineuronal nets, including the proteoglycans aggrecan, brevican, and neurocan. Finally, it introduces current concepts on the function of perineuronal nets that are specifically based on experimental data collected in the superior olivary complex and point to a contribution of perineuronal nets to synaptic transmission and neuronal excitability.

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Brevican-containing perineuronal nets of extracellular matrix in dissociated hippocampal primary cultures

Molecular and Cellular Neuroscience ◽

10.1016/j.mcn.2006.01.011 ◽

2006 ◽

Vol 31 (4) ◽

pp. 774-784 ◽

Cited By ~ 72

Author(s):

Nora John ◽

Hans Krügel ◽

Renato Frischknecht ◽

Karl-Heinz Smalla ◽

Christian Schultz ◽

...

Keyword(s):

Extracellular Matrix ◽

Primary Cultures ◽

Perineuronal Nets

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Microglia as hackers of the matrix: sculpting synapses and the extracellular space

Cellular and Molecular Immunology ◽

10.1038/s41423-021-00751-3 ◽

2021 ◽

Author(s):

Joshua D. Crapser ◽

Miguel A. Arreola ◽

Kate I. Tsourmas ◽

Kim N. Green

Keyword(s):

Extracellular Matrix ◽

Extracellular Space ◽

The Other ◽

Perineuronal Nets ◽

Normal Brain ◽

The Matrix ◽

Health And Disease ◽

Synapse Model ◽

Brain Homeostasis

AbstractMicroglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise the four elements of the contemporary tetrapartite synapse model. While research in this area is still just beginning, accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis, and such processes may, in turn, become dysfunctional in disease. As it relates to synapses, microglia are reported to modify the perisynaptic matrix, which is the diffuse matrix that surrounds dendritic and axonal terminals, as well as perineuronal nets (PNNs), specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses. The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other, and microglia may need to sculpt the matrix to modify the synapses within. Here, we provide an overview of the microglial regulation of synapses, perisynaptic matrix, and PNNs, propose candidate mechanisms by which these structures may be modified, and present the implications of such modifications in normal brain homeostasis and in disease.

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Axon initial segment ensheathed by extracellular matrix in perineuronal nets

Neuroscience ◽

10.1016/j.neuroscience.2005.11.068 ◽

2006 ◽

Vol 138 (2) ◽

pp. 365-375 ◽

Cited By ~ 58

Author(s):

G. Brückner ◽

S. Szeöke ◽

S. Pavlica ◽

J. Grosche ◽

J. Kacza

Keyword(s):

Extracellular Matrix ◽

Initial Segment ◽

Axon Initial Segment ◽

Perineuronal Nets

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Perineuronal nets — a specialized form of extracellular matrix in the adult nervous system

Brain Research Reviews ◽

10.1016/0165-0173(94)90006-x ◽

1994 ◽

Vol 19 (1) ◽

pp. 128-145 ◽

Cited By ~ 263

Author(s):

Marco R. Celio ◽

Ingmar Blumcke

Keyword(s):

Extracellular Matrix ◽

Nervous System ◽

Perineuronal Nets ◽

Specialized Form

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Neuron-Glia Interactions in Neural Plasticity: Contributions of Neural Extracellular Matrix and Perineuronal Nets

Neural Plasticity ◽

10.1155/2016/5214961 ◽

2016 ◽

Vol 2016 ◽

pp. 1-14 ◽

Cited By ~ 65

Author(s):

Egor Dzyubenko ◽

Christine Gottschling ◽

Andreas Faissner

Keyword(s):

Extracellular Matrix ◽

Neural Plasticity ◽

Signal Transmission ◽

Perineuronal Nets ◽

Molecular Scaffold ◽

Macromolecular Assemblies ◽

Neuropsychiatric Diseases ◽

The Central Nervous System ◽

And Function

Synapses are specialized structures that mediate rapid and efficient signal transmission between neurons and are surrounded by glial cells. Astrocytes develop an intimate association with synapses in the central nervous system (CNS) and contribute to the regulation of ion and neurotransmitter concentrations. Together with neurons, they shape intercellular space to provide a stable milieu for neuronal activity. Extracellular matrix (ECM) components are synthesized by both neurons and astrocytes and play an important role in the formation, maintenance, and function of synapses in the CNS. The components of the ECM have been detected near glial processes, which abut onto the CNS synaptic unit, where they are part of the specialized macromolecular assemblies, termed perineuronal nets (PNNs). PNNs have originally been discovered by Golgi and represent a molecular scaffold deposited in the interface between the astrocyte and subsets of neurons in the vicinity of the synapse. Recent reports strongly suggest that PNNs are tightly involved in the regulation of synaptic plasticity. Moreover, several studies have implicated PNNs and the neural ECM in neuropsychiatric diseases. Here, we highlight current concepts relating to neural ECM and PNNs and describe anin vitroapproach that allows for the investigation of ECM functions for synaptogenesis.

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