Chondroitin sulfate demarcates astrocytic territories in the mammalian cerebral cortex

doi:10.1016/j.neulet.2010.07.064

Neuroscience Letters

Volume 483, Issue 1, 8 October 2010, Pages 67-72

https://doi.org/10.1016/j.neulet.2010.07.064 Get rights and content

Abstract

Adjacent astrocytes in the grey matter of the mammalian cerebral cortex are organized in a tile-like manner and separated from one another, forming discrete domains named “non-overlapping territories”. We have previously reported that an anti-chondroitin sulfate (CS) antibody, CS-56, marks a subpopulation of cortical astrocytes which we named the dandelion clock-like structure (DACS) based on its morphological characteristics. In the present study, we found that another anti-CS antibody (anti-CS-C) was also able to detect the DACS and the morphological analysis revealed that a single DACS enwrapped five to six neuronal somata on average, which indicated that DACS coincided with a single astrocyte territory. Double labeling of CS-C and glial fibrillary acidic protein (GFAP) showed a slight overlap between the two territories in the adult cerebral cortex of mice. The neuron number enwrapped by a single DACS was unchanged between 3- and 7-week-old mice, while more extensive processes of DACSs were found in 7-week-old mice compared with those in 3-week-old ones. Moreover, the measurement of a single DACS area was significantly increased by 45% between 3- and 7-week-old mice. In addition, DACSs were found in human, monkey, and domestic pig brains, but not mallard ones, indicating that DACS was conserved in mammalian species. Taken together, CS demarcates territories of a certain population of cortical astrocytes and the cerebral cortex is composed of CS-rich astrocytes and -poor astrocytes in a mosaic fashion.

Section snippets

Acknowledgement

This work was supported in part by a grant-in-aid from the Japanese Ministry of Education, Culture, Sports, Science and Technology.

References (15)

T. Fellin et al.
Neuronal synchrony mediated by astrocytic glutamate through activation of extrasynaptic NMDA receptors
Neuron
(2004)
N. Hayashi et al.
Attenuation of glial scar formation in the injured rat brain by heparin oligosaccharides
Neurosci. Res.
(2004)
N. Hayashi et al.
DACS, novel matrix structure composed of chondroitin sulfate proteoglycan in the brain
Biochem. Biophys. Res. Commun.
(2007)
M. Nedergaard et al.
New roles for astrocytes: redefining the functional architecture of the brain
Trends Neurosci.
(2003)
W. Walz et al.
Immunocytochemical evidence for a distinct GFAP-negative subpopulation of astrocytes in the adult rat hippocampus
Neurosci. Lett.
(1998)
E.J. Bradbury et al.
Chondroitinase ABC promotes functional recovery after spinal cord injury
Nature
(2002)
E.A. Bushong et al.
Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains
J. Neurosci.
(2002)

There are more references available in the full text version of this article.

Cited by (15)

Comparative Anatomy of Glial Cells in Mammals
2020, Evolutionary Neuroscience
Neuron-supporting glial cells display a considerable variability in phenotype and function. The first part of the chapter describes general principles of glial cell phenotype and distribution including evolution of glia-mediated neuronal support, glial morphology according to the types of cell processes, glial morphology in development, and glioneuronal domains of information processing at various hierarchical levels. The second part describes in more detail the various phenotypes and functions of glial cells in the mammalian central and peripheral nervous systems.
The tetrapartite synapse: a key concept in the pathophysiology of schizophrenia
2018, European Psychiatry
Citation Excerpt :
Their morphology may vary across brain regions, but in general they present as round rosettes of diffuse immunolabeling, with an overall diameter of 100–200 μm, often organized in short, dense segments. Several dendrites, and occasionally some neuronal and glial cell bodies are embedded in these clusters, while several glial cells surround them (Chelini et al; unpublished observations) [135,137]. In the mouse brain, CS-6/Glia clusters were found to develop in late postnatal development, suggesting a role in regulation of synaptic connectivity similar to that shown for PNNs [135,137–141].
Growing evidence points to synaptic pathology as a core component of the pathophysiology of schizophrenia (SZ). Significant reductions of dendritic spine density and altered expression of their structural and molecular components have been reported in several brain regions, suggesting a deficit of synaptic plasticity. Regulation of synaptic plasticity is a complex process, one that requires not only interactions between pre- and post-synaptic terminals, but also glial cells and the extracellular matrix (ECM). Together, these elements are referred to as the ‘tetrapartite synapse’, an emerging concept supported by accumulating evidence for a role of glial cells and the extracellular matrix in regulating structural and functional aspects of synaptic plasticity. In particular, chondroitin sulfate proteoglycans (CSPGs), one of the main components of the ECM, have been shown to be synthesized predominantly by glial cells, to form organized perisynaptic aggregates known as perineuronal nets (PNNs), and to modulate synaptic signaling and plasticity during postnatal development and adulthood. Notably, recent findings from our group and others have shown marked CSPG abnormalities in several brain regions of people with SZ. These abnormalities were found to affect specialized ECM structures, including PNNs, as well as glial cells expressing the corresponding CSPGs. The purpose of this review is to bring forth the hypothesis that synaptic pathology in SZ arises from a disruption of the interactions between elements of the tetrapartite synapse.
Comparative Anatomy of Glial Cells in Mammals
2016, Evolution of Nervous Systems: Second Edition
Neuron-supporting glial cells display a considerable variability in phenotype and function. The first part of the chapter describes general principles of glial cell phenotype and distribution including evolution of glia-mediated neuronal support, glial morphology according to the types of cell processes, glial morphology in development, and glioneuronal domains of information processing at various hierarchical levels. The second part describes in more detail the various phenotypes and functions of glial cells in the mammalian central and peripheral nervous systems.
Chondroitin sulfate proteoglycan tenascin-R regulates glutamate uptake by adult brain astrocytes
2014, Journal of Biological Chemistry
Citation Excerpt :
Consistent with this possibility, TNR is up-regulated in astrogliosis (51, 52). The DACS becomes visible as postnatal cortical development proceeds (16). Expression levels of astrocytic glutamate transporters (GLAST and GLT-1) increase during postnatal development (53, 54), whereas null mutations of these transporters impair metabolic cross-talk between astrocytes and neurons, and thereby affect synaptic activities (55).
In our previous study, the CS-56 antibody, which recognizes a chondroitin sulfate moiety, labeled a subset of adult brain astrocytes, yielding a patchy extracellular matrix pattern. To explore the molecular nature of CS-56-labeled glycoproteins, we purified glycoproteins of the adult mouse cerebral cortex using a combination of anion-exchange, charge-transfer, and size-exclusion chromatographies. One of the purified proteins was identified as tenascin-R (TNR) by mass spectrometric analysis. When we compared TNR mRNA expression patterns with the distribution patterns of CS-56-positive cells, TNR mRNA was detected in CS-56-positive astrocytes. To examine the functions of TNR in astrocytes, we first confirmed that cultured astrocytes also expressed TNR protein. TNR knockdown by siRNA expression significantly reduced glutamate uptake in cultured astrocytes. Furthermore, expression of mRNA and protein of excitatory amino acid transporter 1 (GLAST), which is a major component of astrocytic glutamate transporters, was reduced by TNR knockdown. Our results suggest that TNR is expressed in a subset of astrocytes and contributes to glutamate homeostasis by regulating astrocytic GLAST expression.
Precursor Cell Biology and the Development of Astrocyte Transplantation Therapies: Lessons from Spinal Cord Injury
2011, Neurotherapeutics
This review summarizes current progress on development of astrocyte transplantation therapies for repair of the damaged central nervous system. Replacement of neurons in the injured or diseased central nervous system is currently one of the most popular therapeutic goals, but if neuronal replacement is attempted in the absence of appropriate supporting cells (astrocytes and oligodendrocytes), then the chances of restoring neurological functional are greatly reduced. Although the past 20 years have offered great progress on oligodendrocyte replacement therapies, astrocyte transplantation therapies have been both less explored and comparatively less successful. We have now developed successful astrocyte transplantation therapies by pre-differentiating glial restricted precursor (GRP) cells into a specific population of GRP cell-derived astrocytes (GDAs) by exposing the GRP cells to bone morphogenetic protein-4 (BMP) prior to transplantation. When transplanted into transected rat spinal cord, rat and human GDAs^BMP promote extensive axonal regeneration, rescue neuronal cell survival, realign tissue structure, and restore behavior to pre-injury levels on a grid-walk analysis of volitional foot placement. Such benefits are not provided by GRP cells themselves, demonstrating that the lesion environment does not direct differentiation in a manner optimally beneficial for the restoration of function. Such benefits also are not provided by transplantation of a different population of astrocytes generated from GRP cells exposed to ciliary neurotrophic factor (GDAs^CNTF), thus providing the first transplantation-based evidence of functional heterogeneity in astrocyte populations. Moreover, lessons learned from the study of rat cells are strongly predictive of outcomes using human cells. Thus, these studies provide successful strategies for the use of astrocyte transplantation therapies for restoration of function following spinal cord injury.
Molecular signature of extracellular matrix pathology in schizophrenia
2021, European Journal of Neuroscience

View all citing articles on Scopus

View full text

Chondroitin sulfate demarcates astrocytic territories in the mammalian cerebral cortex

Abstract

Section snippets

Acknowledgement

Neuron

Neurosci. Res.

Biochem. Biophys. Res. Commun.

Trends Neurosci.

Neurosci. Lett.

Chondroitinase ABC promotes functional recovery after spinal cord injury

Nature

Protoplasmic astrocytes in CA1 stratum radiatum occupy separate anatomical domains

J. Neurosci.