Glucocorticoid and Excitatory Insult Opposingly Regulate Nogo-A and GAP-43 Expressions to Promote Neurite Outgrowth in Injured Dorsal Root Ganglion Neurons

Shih-Ying Tsai ； Yi-Hsuan Lee

《Adaptive Medicine》 3卷1期 (2011/04) Pp. 32-40

https://doi.org/10.4247/AM.2011.ABB001

並列摘要

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.

並列關鍵字

corticosterone ； GAP-43 ； Nogo-A, protein kinase C ； RhoA ； Rho kinase ； neurite outgrowth ； dorsal root ganglion neurons