Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex (original) (raw)
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DACS, novel matrix structure composed of chondroitin sulfate proteoglycan in the brain
Biochemical and Biophysical Research Communications, 2007
Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix (ECM) in the brain. In the adult cerebral cortex, there are special CSPG-containing structures known as perineuronal nets (PNNs), which are highly condensed ECM structures. Here, we report a novel CSPG-containing structure distinct from PNNs in the adult mouse cerebral cortex. An anti-chondroitin sulfate antibody CS56 delineated a structure with a unique morphology like a dandelion clock. Accordingly, we named it DAndelion Clock-like Structure (DACS). Immunohistochemical evidence showed that DACSs surrounded a group of NeuN-positive/GABA-negative neurons. At ultrastructural level, CS56-immunoreactivities were localized in the cytoplasm and on the membrane of astrocytes. As the postnatal cerebral cortex matured, DACSs became visible around the end of the critical period. This is the first report demonstrating the presence of an ECM structure DACS composed of CSPGs around a group of cortical neurons in the adult cerebral cortex.
Experimental Brain Research, 1998
Lattice-like perineuronal accumulations of extracellular-matrix proteoglycans have been shown to develop during postnatal maturation and to persist throughout life as perineuronal nets (PNs) in many brain regions. However, the dynamics of their reorganization in adults are as yet unknown. The aim of the present study was to examine the capability of PNs for reconstitution after experimental destruction and to search for possible consequences of extracellular-matrix degradation for neurons and glial cells. The changes were induced by single intracortical injections of Proteus vulgaris chondroitinase ABC and studied after postinjection periods of 1 day to 5 months. The N-acetylgalactosamine-binding Wisteria floribunda agglutinin (WFA), an antibody against chondroitin-sulphate proteoglycans, three antibodies recognizing initial chondroitin or chondroitin-sulphate moieties (`stubs') of proteoglycan core proteins, an antibody against the hyaluronan-binding protein component of versican, and biotinylated hyaluronectin, which binds to hyaluronan, were used as cytochemical markers. One day postinjection, the WFA-binding sites and hyaluronan were shown to be almost completely removed within a circumscribed digestion zone. The staining of different core-protein components revealed only fragments of PNs. These changes were found to be partly compensated 4 weeks after injection of chondroitinase ABC. After 8 and 12 weeks postinjection, the cytochemical and structural characteristics as well as the area-specific distribution patterns of PNs were progressively reconstituted. At 5 months postinjection, they could not be distinguished from those in untreated tissue. In contrast to such transient changes, a diffuse chondroitin-sulphate proteoglycan immunoreactivity persisted in the neuropil. Loss of neurons or alterations of their structure as well as reactions of glial cells were not observed. We conclude from this study that PNs, enzymatically destroyed in the adult rat brain, can be completely reconstituted, but the restoration of their extracellular-matrix components needs several months.
The brain extracellular matrix (ECM) is a proteoglycan complex that occupies the extracellular space between brain cells and regulates brain development, brain wiring, and synaptic plasticity. However, the action of the ECM on synaptic plasticity remains controversial. Here, we employed serial section electron microscopy to show that enzymatic attenuation of ECM with chondroitinase ABC (ChABC) triggers the appearance of new glutamatergic synapses onto thin dendritic spines of CA1 pyramidal neurons. The appearance of new synapses increased the ratio of the field excitatory postsynaptic potential (fEPSP) to presynaptic fiber volley (PrV), suggesting that these new synapses are formed on existing axonal fibers. However, both the mean miniature excitatory postsynaptic current (mEPSC) amplitude and AMPA/NMDA ratio were decreased, suggesting that ECM attenuation increased the proportion of ‘unpotentiated’ synapses. A higher proportion of unpotentiated synapses would be expected to promote...
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1993
Extracellular matrix (ECM) is a secreted extracellular network. Few components of adult brain ECM are known. We have identified a new, large chondroitin sulfate proteoglycan (T1 antigen) that acts like a general ECM protein of brain. First, it is present throughout the brain; second, it has the properties of an extracellular protein; and third, it is extracted only under denaturing conditions. Immunocytochemical localization of the T1 antigen by light microscope shows it to be present throughout the rat brain in both white and gray matter. The T1 antigen outlines Purkinje and other large cells. No antigenicity is seen inside these cells. Biochemical evidence suggests that the T1 antigen is extracellular rather than cytosolic or intravesicular. The T1 antigen is disulfide-linked to two other proteins. Disulfide bonds are found only in extracellular or intravesicular proteins, not in intracellular cytosolic proteins. Moreover, the T1 antigen is probably not intravesicular. Unlike intr...
Neural Plasticity, 2015
It is currently known that in CNS the extracellular matrix is involved in synaptic stabilization and limitation of synaptic plasticity. However, it has been reported that the treatment with chondroitinase following injury allows the formation of new synapses and increased plasticity and functional recovery. So, we hypothesize that some components of extracellular matrix may modulate synaptic transmission. To test this hypothesis we evaluated the effects of chondroitin sulphate (CS) on excitatory synaptic transmission, cellular excitability, and neuronal plasticity using extracellular recordings in the CA1 area of rat hippocampal slices. CS caused a reversible depression of evoked field excitatory postsynaptic potentials in a concentration-dependent manner. CS also reduced the population spike amplitude evoked after orthodromic stimulation but not when the population spikes were antidromically evoked; in this last case a potentiation was observed. CS also enhanced paired-pulse facilitation and long-term potentiation. Our study provides evidence that CS, a major component of the brain perineuronal net and extracellular matrix, has a function beyond the structural one, namely, the modulation of synaptic transmission and neuronal plasticity in the hippocampus.
Developmental …, 2007
CITATIONS 126 READS 88 6 authors, including: Some of the authors of this publication are also working on these related projects: Effects of the glycan polysialic acid on prefrontal cortex synaptic plasticity and learning View project Alexander Dityatev Deutsches Zentrum für Neurodegenerative Erk… 138 PUBLICATIONS 5,820 CITATIONS SEE PROFILE Ralf Kleene University of Hamburg 59 PUBLICATIONS 1,791 CITATIONS SEE PROFILE All content following this page was uploaded by Alexander Dityatev on 17 December 2013.
Chondroitin Sulfates in Axon Regeneration and Plasticity
Trends in Glycoscience and Glycotechnology, 2011
Chondroitin sulfate proteoglycans (CSPGs) are large extracellular matrix molecules which are highly upregulated in the glial scar after injury to the nervous system. They are mostly inhibitory and have been shown to hinder regeneration of axons across lesions. The removal of CPSGs with bacterial enzyme chondroitinase ABC improves axonal regeneration. In addition, CSPGs are a major component of perineuronal nets, which control plasticity in the CNS, and their removal enhances structural plasticity resulting in an increase in functional recovery. In this review, we shall discuss the role of CSPGs in axonal regeneration and plasticity after nervous system injury and how recent discoveries of CSPG receptors and interacting partners may shed new insights onto the function of these inhibitory molecules.
Targeting the neural extracellular matrix in neurological disorders
Neuroscience, 2013
The extracellular matrix (ECM) is known to regulate important processes in neuronal cell development, activity and growth. It is associated with the structural stabilization of neuronal processes and synaptic contacts during the maturation of the central nervous system. The remodeling of the ECM during both development and after central nervous system injury has been shown to affect neuronal guidance, synaptic plasticity and their regenerative responses. Particular interest has focused on the inhibitory role of chondroitin sulfate proteoglycans (CSPGs) and their formation into dense lattice-like structures, termed perineuronal nets (PNNs), which enwrap sub-populations of neurons and restrict plasticity. Recent studies in mammalian systems have implicated CSPGs and PNNs in regulating and restricting structural plasticity. The enzymatic degradation of CSPGs or destabilization of PNNs has been shown to enhance neuronal activity and plasticity after central nervous system injury. This review focuses on the role of the ECM, CSPGs and PNNs; and how developmental and pharmacological manipulation of these structures have enhanced neuronal plasticity and aided functional recovery in regeneration, stroke, and amblyopia. In addition to CSPGs, this review also points to the functions and potential therapeutic value of these and several other key ECM molecules in epileptogenesis and dementia.