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Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes
Author(s) -
Liu WeiLin,
Lee YiHsuan,
Tsai ShihYing,
Hsu Chung Yi,
Sun YuYo,
Yang LiangYo,
Tsai ShingHan,
Yang WeiChung Vivian
Publication year - 2008
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20706
Subject(s) - chondroitin sulfate proteoglycan , glial fibrillary acidic protein , glial scar , astrocyte , neurite , ampa receptor , biology , neuroprotection , gliosis , microbiology and biotechnology , neuroglia , glutamate receptor , neuroscience , immunology , biochemistry , receptor , proteoglycan , central nervous system , immunohistochemistry , in vitro , extracellular matrix
Abstract Reactive gliosis caused by post‐traumatic injury often results in marked expression of chondroitin sulfate proteoglycan (CSPG), which inhibits neurite outgrowth and regeneration. Methylprednisolone (MP), a synthetic glucocorticoid, has been shown to have neuroprotective and anti‐inflammatory effects for the treatment of acute spinal cord injury (SCI). However, the effect of MP on CSPG expression in reactive glial cells remains unclear. In our study, we induced astrocyte reactivation using α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA) and cyclothiazide to mimic the excitotoxic stimuli of SCI. The expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivation, and CSPG neurocan and phosphacan were significantly elevated by AMPA treatment. The conditioned media from AMPA‐treated astrocytes strongly inhibited neurite outgrowth of rat dorsal root ganglion neurons, and this effect was reversed by pretreatment with MP. Furthermore, MP downregulated GFAP and CSPG expression in adult rats with SCI. Additionally, both the glucocorticoid receptor (GR) antagonist RU486 and GR siRNA reversed the inhibitory effects of MP on GFAP and neurocan expression. Taken together, these results suggest that MP may improve neuronal repair and promote neurite outgrowth after excitotoxic insult via GR‐mediated downregulation of astrocyte reactivation and inhibition of CSPG expression. © 2008 Wiley‐Liss, Inc.