Methylprednisolone inhibits the expression of glial fibrillary acidic protein and chondroitin sulfate proteoglycans in reactivated astrocytes.
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 alpha-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.
Liu
Wei-Lin
WL
Graduate Institute of Biomedical Materials and Engineering, Taipei Medical University, Taipei, Taiwan.
Lee
Yi-Hsuan
YH
Tsai
Shih-Ying
SY
Hsu
Chung Yi
CY
Sun
Yu-Yo
YY
Yang
Liang-Yo
LY
Tsai
Shing-Han
SH
Yang
Wei-Chung Vivian
WC
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D011508:Chondroitin Sulfate Proteoglycans / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005904:Glial Fibrillary Acidic Protein / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D008775:Methylprednisolone / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D011508:Chondroitin Sulfate Proteoglycans; D005904:Glial Fibrillary Acidic Protein; D008775:Methylprednisolone