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題 名 | Glucocorticoid and Excitatory Insult Opposingly Regulate Nogo-A and GAP-43 Expressions to Promote Neurite Outgrowth in Injured Dorsal Root Ganglion Neurons |
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作 者 | Tsai, Shih-ying; Lee, Yi-hsuan; | 書刊名 | Adaptive Medicine |
卷 期 | 3:1 2011.04[民100.04] |
頁 次 | 頁32-40 |
分類號 | 415.114 |
關鍵詞 | Corticosterone; GAP-43; Nogo-A; Protein kinase C; RhoA; Rho kinase; Neurite outgrowth; Dorsal root ganglion neurons; |
語 文 | 英文(English) |
英文摘要 | In the previous study, we demonstrated that corticosterone (CORT), a stress hormone elevated during neurotrauma, promotes neurite outgrowth in axotomized rat dorsal root ganglion (AX-DRG) neurons when applied prior to the kainic acid (KA) treatment, which mimics excitotoxic insult. In this study, we showed that this combined stress condition (CORT+KA) increased neurite outgrowth and GAP-43 immunoreactivity in AX-DRG neurons, and the effect were reversed by glucocorticoid receptor (GR) antagonist RU486, mineralcorticoid receptor antagonist spironolactone, and AMPA/KA receptor antagonist CNQX. Protein kinase C (PKC) inhibitor RO-318220 reduced the CORT+KA-enhanced neurite growth when applied prior to KA but not to the CORT treatment. On the other hand, growth-inhibitory protein Nogo-A and its downstream signaling protein RhoA were both down-regulated by CORT treatment in DRG neurons in a GR-dependent manner. Blockade of Rho kinase (ROCK) activity by Y-274632 showed growthpromoting effect but did not further facilitate the CORT+KA-promoted neurite growth. Together, these results suggest that the nerve injury-associated stress and excitatory insult may contribute to the nerve regeneration by suppression of the Nogo-A/RhoA/ROCK signaling pathway and activation of the AMPA/KA receptor- and PKC-dependent GAP-43 expression. |
本系統中英文摘要資訊取自各篇刊載內容。