The brain chondroitin sulfate proteoglycan brevican associates with astrocytes ensheathing cerebellar glomeruli and inhibits neurite outgrowth from granule neurons

Hidekazu Yamada, Barbara Fredette, Kenya Shitara, Kazuki Hagihara, Ryu Miura, Barbara Ranscht, William B. Stallcup, Yu Yamaguchi

Research output: Contribution to journalArticlepeer-review

191 Citations (Scopus)

Abstract

Brevican is a nervous system-specific chondroitin sulfate proteoglycan that belongs to the aggrecan family and is one of the most abundant chondroitin sulfate proteoglycans in adult brain. To gain insights into the role of brevican in brain development, we investigated its spatiotemporal expression, cell surface binding, and affects on neurite outgrowth, using rat cerebellar cortex as a model system. Immunoreactivity of brevican occurs predominantly in the protoplasmic islet in the internal granular layer after the third postnatal week. Immunoelectron microscopy revealed that brevican is localized in close association with the surface of astrocytes that form neuroglial sheaths of cerebellar glomeruli where incoming mossy fibers interact with dendrites and axons from resident neurons. In situ hybridization showed that brevican is synthesized by these astrocytes themselves. In primary cultures of cerebellar astrocytes, brevican is detected on the surface of these cells. Binding assays with exogenously added brevican revealed that primary astrocytes and several immortalized neural cell lines have cell surface binding sites for brevican cora protein. These cell surface brevican binding sites recognize the C-terminal portion of the core protein and are independent of cell surface hyaluronan. These results indicate that brevican is synthesized by astrocytes and retained on their surface by an interaction involving its core protein. Purified brevican inhibits neurite outgrowth from cerebellar granule neurons in vitro, an activity that requires chondroitin sulfate chains. We suggest that brevican presented on the surface of neuroglial sheaths may be controlling the infiltration of axons and dendrites into maturing glomeruli.

Original languageEnglish
Pages (from-to)7784-7795
Number of pages12
JournalJournal of Neuroscience
Volume17
Issue number20
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Astrocytes
  • Brevican
  • Cerebellar development
  • Chondroitin sulfate proteoglycan
  • Glomerulus
  • Neurite outgrowth

ASJC Scopus subject areas

  • Neuroscience(all)

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