Human Molecular Genetics Department, Institute of Molecular Genetics, Russian Academy of Sciences, Moscow, The Russian Federation.
Cell Mol Neurobiol. 2010 Jan;30(1):71-9. doi: 10.1007/s10571-009-9432-0. Epub 2009 Jul 25.
Consisting of a fragment of ACTH(4-7) and C-terminal PGP tripeptide, the polypeptide Semax is successfully used for acute stroke therapy. Previous experiments showed rapid induction of Bdnf, Ngf, and TrkB expression in intact rat hippocampus following Semax treatment. To investigate the mRNA expression of neurotrophins and their receptors after treatment with either Semax or PGP, the rat brains were analyzed at three time points following a permanent middle cerebral artery occlusion (pMCAO). We have shown for the first time that both Semax and PGP activate the transcription of neurotrophins and their receptors in the cortex of rats subjected to pMCAO. The profiles of transcription alteration under PGP and Semax treatment were partially overlapped. Semax enhanced the transcription of Bdnf, TrkC, and TrkA 3 h after occlusion, Nt-3 and Ngf 24 h after occlusion, and Ngf 72 h after occlusion. PGP enhanced the transcription of Bdnf and TrkC 3 h after pMCAO and Ngf, TrkB, TrkC, and TrkA 24 h after pMCAO. The analysis of the transcription alterations under PGP and Semax treatment in the cortex of rats without surgery, sham-operated rats and rats subjected to pMCAO revealed that Semax selectively affected the transcription of neurotrophins and their receptors in the ischemic rat cortex, whereas the influence of PGP was mainly unspecific.
由 ACTH(4-7)片段和 C 端 PGP 三肽组成的多肽 Semax 成功地用于急性中风治疗。先前的实验表明，在 Semax 处理后，完整大鼠海马体中 Bdnf、Ngf 和 TrkB 的表达迅速诱导。为了研究 Semax 或 PGP 处理后神经营养因子及其受体的 mRNA 表达，在永久性大脑中动脉闭塞（pMCAO）后三个时间点分析大鼠大脑。我们首次表明，无论是 Semax 还是 PGP，都能激活 pMCAO 大鼠皮质中神经营养因子及其受体的转录。PGP 和 Semax 处理下转录改变的特征部分重叠。Semax 在闭塞后 3 小时增强了 Bdnf、TrkC 和 TrkA 的转录，在闭塞后 24 小时增强了 Nt-3 和 Ngf 的转录，在闭塞后 72 小时增强了 Ngf 的转录。PGP 在 pMCAO 后 3 小时增强了 Bdnf 和 TrkC 的转录，在 pMCAO 后 24 小时增强了 Ngf、TrkB、TrkC 和 TrkA 的转录。在未手术、假手术和 pMCAO 大鼠皮质中进行 PGP 和 Semax 处理下的转录改变分析表明，Semax 选择性地影响缺血性大鼠皮质中神经营养因子及其受体的转录，而 PGP 的影响主要是非特异性的。
