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Russell T Matthews - One of the best experts on this subject based on the ideXlab platform.
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the protein tyrosine phosphatase rptpζ phosphacan is critical for Perineuronal Net structure
Journal of Biological Chemistry, 2020Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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The protein tyrosine phosphatase RPTPζ/phosphacan is critical for Perineuronal Net structure
The Journal of biological chemistry, 2019Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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Development/Plasticity/Repair Sensory Deprivation Alters Aggrecan and Perineuronal Net Expression in the Mouse Barrel Cortex
2016Co-Authors: Paulette A Mcrae, Mary M Rocco, Joshua C Brumberg, Gail Kelly, Russell T MatthewsAbstract:An important role for the neural extracellular matrix in modulating cortical activity-dependent synaptic plasticity has been established by a number of recent studies. However, identification of the critical molecular components of the neural matrix that mediate these processes is far fromcomplete. Of particular interest is the Perineuronal Net (PN), an extracellularmatrix component found surrounding the cell bodyandproximalneurites of a subset ofneurons.Becauseof the appositionof thePN to synapses andexpressionof this structure coincident with the close of the critical period, it has been hypothesized that Nets could play uniquely important roles in synapse stabilization and maturation. Interestingly, previous work has also shown that expression of PNs is dependent on appropriate sensory stimulation in the visual system. Here, we investigated whether PNs in the mouse barrel cortex are expressed in an activity-dependent manner bymanipulating sensory input throughwhisker trimming. Importantly, thismanipulationdidnot lead to a global loss of PNsbut instead led to a specific decrease inPNs, detectedwith the antibodyCat-315, in layer IVof thebarrel cortex. In addition,we identified akey activity-regulated component of PNs is the proteoglycan aggrecan.We also demonstrate that these Cat-315-positive neurons virtually all also express parvalbumin. Together, these data are in support of an important role for aggrecan in the activity-dependent formation of PNs on parvalbumin-expressing cells and suggest a role for expression of these Nets in regulating the close of the critical period. Key words: chondroitin sulfate; lectican; extracellular matrix; proteoglycan; parvalbumin; somatosensory cortex; critical perio
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Reorganization of Synaptic Connections and Perineuronal Nets in the Deep Cerebellar Nuclei of Purkinje Cell Degeneration Mutant Mice.
Neural plasticity, 2015Co-Authors: Maren Blosa, Solveig Weigel, Russell T Matthews, Carsten Jäger, Th. Arendt, C. Bursch, Max Holzer, Carsten Janke, Markus MorawskiAbstract:The Perineuronal Net (PN) is a subtype of extracellular matrix appearing as a Net-like structure around distinct neurons throughout the whole CNS. PNs surround the soma, proximal dendrites, and the axonal initial segment embedding synaptic terminals on the neuronal surface. Different functions of the PNs are suggested which include support of synaptic stabilization, inhibition of axonal sprouting, and control of neuronal plasticity. A number of studies provide evidence that removing PNs or PN-components results in renewed neurite growth and synaptogenesis. In a mouse model for Purkinje cell degeneration, we examined the effect of deafferentation on synaptic remodeling and modulation of PNs in the deep cerebellar nuclei. We found reduced GABAergic, enhanced glutamatergic innervations at PN-associated neurons, and altered expression of the PN-components brevican and hapln4. These data refer to a direct interaction between ECM and synapses. The altered brevican expression induced by activated astrocytes could be required for an adequate regeneration by promoting neurite growth and synaptogenesis.
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Deconstructing the Perineuronal Net: cellular contributions and molecular composition of the neuronal extracellular matrix.
Neuroscience, 2012Co-Authors: Ka Giamanco, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are lattice-like substructures of the neural extracellular matrix that enwrap particular populations of neurons throughout the central nervous system. Previous work suggests that this structure plays a major role in modulating developmental neural plasticity and brain maturation. Understanding the precise role of these structures has been hampered by incomplete comprehension of their molecular composition and cellular contributions to their formation, which is studied herein using primary cortical cell cultures. By defining culture conditions to reduce (cytosine-β-d-arabinofuranoside/AraC addition) or virtually eliminate (elevated potassium chloride (KCl) and AraC application) glia, PNN components impacted by this cell type were identified. Effects of depolarizing KCl concentrations alone were also assessed. Our work identified aggrecan as the primary neuronal component of the PNN and its expression was dramatically up-regulated by both depolarization and glial cell inhibition and additionally, the development of aggrecan-positive PNNs was accelerated. Surprisingly, most of the other PNN components tested were made in a glial-dependent manner in our culture system. Interestingly, in the absence of these glial-derived components, an aggrecan- and hyaluronan-reactive PNN developed, demonstrating that these two components are sufficient for base PNN assembly. Other components were expressed in a glial-dependent manner. Overall, this work provides deeper insight into the complex interplay between neurons and glia in the formation of the PNN and improves our understanding of the molecular composition of these structures.
Markus Morawski - One of the best experts on this subject based on the ideXlab platform.
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Neurocan Contributes to Perineuronal Net Development.
Neuroscience, 2020Co-Authors: Sophie Schmidt, Thomas Arendt, Markus Morawski, Mandy SonntagAbstract:Perineuronal Nets (PNs) are matrix molecule assemblies surrounding neuronal somata, dendrites and axon initial segments in a lattice-like appearance. PN molecules are involved in many structural and physiological processes during development and in adulthood, suggesting a crucial role in normal brain function. Neurocan, as one of the main PN proteoglycans, is suggested to control important developmental processes of neuronal tissue. This statement relies on thorough and excellent experimental work mainly conducted in reduced systems, such as cell cultures. However, previous data collected in neurocan-deficient mice do not seem to support neurocan's role in development since brain development in general and the formation of PNs especially in the hippocampus were reported to be undisturbed in neurocan-deficient mice. Here, we aim to re-address the role of neurocan in developmental processes by investigating the influence of neurocan on PN formation in the medial nucleus of the trapezoid body, a PN-enriched nucleus in the auditory brainstem, using neurocan-deficient mice. Immunohistochemical and biochemical analyses demonstrate that neurocan controls the regulation of PN development by influencing mRNA and protein quantity of various PN molecules. Resulting alterations in PN fine structure are critical for PN function as estimated by reduced amount of GAD65/67 and prolongation of synaptic transmission delay of calyx of Held synapses. Thus, neurocan contributes to proper PN formation and synapse physiology in the MNTB.
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the protein tyrosine phosphatase rptpζ phosphacan is critical for Perineuronal Net structure
Journal of Biological Chemistry, 2020Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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The protein tyrosine phosphatase RPTPζ/phosphacan is critical for Perineuronal Net structure
The Journal of biological chemistry, 2019Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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Neuroanatomical characterization of Perineuronal Net components in the human cochlear nucleus and superior olivary complex.
Hearing research, 2018Co-Authors: Luise Weinrich, Thomas Arendt, Mandy Sonntag, Markus MorawskiAbstract:Abstract The human auditory brainstem, especially the cochlear nucleus (CN) and the superior olivary complex (SOC) are characterized by a high density of neurons associated with Perineuronal Nets (PNs). PNs build a specific form of extracellular matrix surrounding the neuronal somata, proximal dendrites and axon initial segments. They restrict synaptic plasticity and control high-frequency synaptic activity, a prominent characteristic of neurons of the auditory brainstem. The distribution of PNs within the auditory brainstem has been investigated in a number of mammalian species. However, much less is known regarding PNs in the human auditory brainstem. The present study aimed at the immunohistochemical identification of PNs in the cochlear nucleus (CN) and superior olivary complex (SOC) in the human brainstem. We focused on the complex nature and molecular variability of PNs in the CN and SOC by using specific antibodies against the main PN components (aggrecan, brevican, neurocan and hyaluronan and proteoglycan link protein 1). Virtually all subnuclei within the ventral CN and SOC were found to be associated with PNs. Direct comparison between gerbil and human yielded similar fine structure of PNs and confirmed the typical tight interdigitation of PNs with synaptic terminals in both species. Noticeably, an elaborate combination of immunohistochemical labelings clearly supports the still debated existence of the medial nucleus of trapezoid body (MNTB) in the human brain. In conclusion, the present study demonstrates that PNs form a prominent extracellular structure on CN and SOC neurons in the human brain, potentially stabilizing synaptic contacts, which is in agreement with many other mammalian species.
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aggrecan link protein and tenascin r are essential components of the Perineuronal Net to protect neurons against iron induced oxidative stress
Cell Death and Disease, 2017Co-Authors: Anne Suttkus, Susanne Rohn, Solveig Weigel, Pia Glockner, Thomas Arendt, Markus MorawskiAbstract:In Alzheimer’s disease (AD), different types of neurons and different brain areas show differential patterns of vulnerability towards neurofibrillary degeneration, which provides the basis for a highly predictive profile of disease progression throughout the brain that now is widely accepted for neuropathological staging. In previous studies we could demonstrate that in AD cortical and subcortical neurons are constantly less frequently affected by neurofibrillary degeneration if they are enwrapped by a specialized form of the hyaluronan-based extracellular matrix (ECM), the so called ‘Perineuronal Net’ (PN). PNs are basically composed of large aggregating chondroitin sulphate proteoglycans connected to a hyaluronan backbone, stabilized by link proteins and cross-linked via tenascin-R (TN-R). Under experimental conditions in mice, PN-ensheathed neurons are better protected against iron-induced neurodegeneration than neurons without PN. Still, it remains unclear whether these neuroprotective effects are directly mediated by the PNs or are associated with some other mechanism in these neurons unrelated to PNs. To identify molecular components that essentially mediate the neuroprotective aspect on PN-ensheathed neurons, we comparatively analysed neuronal degeneration induced by a single injection of FeCl3 on four different mice knockout strains, each being deficient for a different component of PNs. Aggrecan, link protein and TN-R were identified to be essential for the neuroprotective properties of PN, whereas the contribution of brevican was negligible. Our findings indicate that the protection of PN-ensheathed neurons is directly mediated by the Net structure and that both the high negative charge and the correct interaction of Net components are essential for their neuroprotective function.
Geoffrey J. Eill - One of the best experts on this subject based on the ideXlab platform.
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the protein tyrosine phosphatase rptpζ phosphacan is critical for Perineuronal Net structure
Journal of Biological Chemistry, 2020Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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The protein tyrosine phosphatase RPTPζ/phosphacan is critical for Perineuronal Net structure
The Journal of biological chemistry, 2019Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
James W. Fawcett - One of the best experts on this subject based on the ideXlab platform.
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Restoring the pattern of Perineuronal Net sulphation corrects age-related memory loss
2020Co-Authors: James W. Fawcett, Joost Verhaagen, Tommaso Pizzorusso, Sylvain Gigout, Angelo Molinari, Yuko Naito-matsui, Sam Hilton, Simona Foscarin, Bart Nieuwenhuis, Lisa M. SaksidaAbstract:Abstract Memory loss is a usual consequence of ageing. In aged brains, Perineuronal Nets (PNNs), which limit neuroplasticity and are implicated in memory, become inhibitory due to decreased 6-sulphation of their glycan chains (C6S). Aged mice show progressive deficits in memory tasks, but removal of PNNs or digestion of their glycans rescued age-related memory loss. Reduction of permissive C6S by transgenic deletion of 6-sulfotransferase led to very early memory loss. However, restoring C6S levels in aged animals by AAV delivery or transgenic expression of 6-sulfotransferase restored memory. Low C6S levels caused loss of cortical long-term potentiation, which was restored by AAV-mediated 6-sulfotransferase delivery. The study shows that loss of C6S in the aged brain leads to declining memory and cognition, which can be restored by C6S replacement. One sentence summary Sulphation changes in Perineuronal Nets lead to age-related memory loss; correction of sulphation restores memory.
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The Chemorepulsive Protein Semaphorin 3A and Perineuronal Net-Mediated Plasticity
Neural plasticity, 2016Co-Authors: F. De Winter, Jessica C. F. Kwok, James W. Fawcett, Daniela Carulli, Joost VerhaagenAbstract: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.
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Perineuronal Net digestionwith chondroitinase restores memory inmice with tau pathology
2014Co-Authors: Sujeong Yang, James W. Fawcett, Matthias Cacquevel, Lisa M. Saksida, Timothy Bussey, Bernard L. Schneider, Patrick Aebischer, Riccardo Melani, Tommaso Pizzorusso, Maria Grazia SpillantiniAbstract:This work was supported by the European Union Framework 7 Project Plasticise (S.Y., M.C., M.G.S., J.W.F., P.R., P.A., B.L.S.), the Wellcome Trust (L.M.S., T.J.B.), the Alzheimer's Research UK (M.G.S.), and the UK Medical Research Council (L.M.S., T.J.B.). J.W.F.'s work is supported by the ERC-ECMneuro, the Christopher and Dana Reeve Foundation and the NIHR Cambridge biomedical research center.
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Perineuronal Net digestion with chondroitinase restores memory in mice with tau pathology.
Experimental neurology, 2014Co-Authors: Sujeong Yang, James W. Fawcett, Matthias Cacquevel, Lisa M. Saksida, Timothy Bussey, Bernard L. Schneider, Patrick Aebischer, Riccardo Melani, Tommaso Pizzorusso, Maria Grazia SpillantiniAbstract:Alzheimer's disease is the most prevalent tauopathy and cause of dementia. We investigate the hypothesis that reactivation of plasticity can restore function in the presence of neuronal damage resulting from tauopathy. We investigated two models with tau hyperphosphorylation, aggregation and neurodegeneration: a transgenic mouse model in which the mutant P301S tau is expressed in neurons (Tg P301S), and a model in which an adeno-associated virus expressing P301S tau (AAV-P301S) was injected in the perirhinal cortex, a region critical for object recognition (OR) memory. Both models show profound loss of OR memory despite only 15% neuronal loss in the Tg P301S and 26% in AAV-P301S-injected mice. Recordings from perirhinal cortex slices of 3 month-old P301S transgenic mice showed a diminution in synaptic transmission following temporal stimulation. Chondroitinase ABC (ChABC) can reactivate plasticity and affect memory through actions on Perineuronal Nets. ChABC was injected into the perirhinal cortex and animals were tested for OR memory 1 week later, demonstrating restoration of OR memory to normal levels. Synaptic transmission indicated by fEPSP amplitude was restored to control levels following ChABC treatment. ChABC did not affect the progression of neurodegenerative tauopathy. These findings suggest that increasing plasticity by manipulation of Perineuronal Nets offers a novel therapeutic approach to the treatment of memory loss in neurodegenerative disorders.
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The Perineuronal Net and the control of CNS plasticity
Cell and tissue research, 2012Co-Authors: Difei Wang, James W. FawcettAbstract:Perineuronal Nets (PNNs) are reticular structures that surround the cell body of many neurones, and extend along their dendrites. They are considered to be a specialized extracellular matrix in the central nervous system (CNS). PNN formation is first detected relatively late in development, as the mature synaptic circuitry of the CNS is established and stabilized. Its unique distribution in different CNS regions, the timing of its establishment, and the changes it undergoes after injury all point toward diverse and important functions that it may be performing. The involvement of PNNs in neuronal plasticity has been extensively studied over recent years, with developmental, behavioural, and functional correlations. In this review, we will first briefly detail the structure and organization of PNNs, before focusing our discussion on their unique roles in neuronal development and plasticity. The PNN is an important regulator of CNS plasticity, both during development and into adulthood. Production of critical PNN components is often triggered by appropriate sensory experiences during early postnatal development. PNN deposition around neurones helps to stabilize the established neuronal connections, and to restrict the plastic changes due to future experiences within the CNS. Disruption of PNNs can reactivate plasticity in many CNSs, allowing activity-dependent changes to once again modify neuronal connections. The mechanisms through which PNNs restrict CNS plasticity remain unclear, although recent advances promise to shed additional light on this important subject.
Mariano S. Viapiano - One of the best experts on this subject based on the ideXlab platform.
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the protein tyrosine phosphatase rptpζ phosphacan is critical for Perineuronal Net structure
Journal of Biological Chemistry, 2020Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.
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The protein tyrosine phosphatase RPTPζ/phosphacan is critical for Perineuronal Net structure
The Journal of biological chemistry, 2019Co-Authors: Geoffrey J. Eill, Markus Morawski, Ashis Sinha, Mariano S. Viapiano, Russell T MatthewsAbstract:Perineuronal Nets (PNNs) are conspicuous neuron-specific substructures within the extracellular matrix of the central nervous system that have generated an explosion of interest over the last decade. These reticulated structures appear to surround synapses on the cell bodies of a subset of the neurons in the central nervous system and play key roles in both developmental and adult-brain plasticity. Despite the interest in these structures and compelling demonstrations of their importance in regulating plasticity, their precise functional mechanisms remain elusive. The limited mechanistic understanding of PNNs is primarily because of an incomplete knowledge of their molecular composition and structure and a failure to identify PNN-specific targets. Thus, it has been challenging to precisely manipulate PNNs to rigorously investigate their function. Here, using mouse models and neuronal cultures, we demonstrate a role of receptor protein tyrosine phosphatase zeta (RPTPζ) in PNN structure. We found that in the absence of RPTPζ, the reticular structure of PNNs is lost and phenocopies the PNN structural abnormalities observed in tenascin-R knockout brains. Furthermore, we biochemically analyzed the contribution of RPTPζ to PNN formation and structure, which enabled us to generate a more detailed model for PNNs. We provide evidence for two distinct kinds of interactions of PNN components with the neuronal surface, one dependent on RPTPζ and the other requiring the glycosaminoglycan hyaluronan. We propose that these findings offer important insight into PNN structure and lay important groundwork for future strategies to specifically disrupt PNNs to precisely dissect their function.