Agapova T Y, Agniullin Y V, Shadrina M I, Shram S I, Slominsky P A, Lymborska S A, Myasoedov N F
Laboratory of Molecular Genetics of Hereditary Diseases, Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics RAS, 2 Kurchatov Sq., Moscow 123182, Russia.
Neurosci Lett. 2007 May 1;417(2):201-5. doi: 10.1016/j.neulet.2007.02.042. Epub 2007 Feb 20.
The heptapeptide Semax, an analogue of the N-terminal adrenocorticotropic hormone fragment (4-10) (ACTH(4-10)), has been shown to exert a number of neuroprotective effects. There are some investigations that connected these effects with the increase of neurotrophin gene expression under the peptide drug application in neuron cell cultures [M.I. Shadrina, O.V. Dolotov, I.A. Grivennikov, P.A. Slominsky, L.A. Andreeva, L.S. Inozemtseva, S.A. Limborska, N.F. Myasoedov, Rapid induction of neurotrophin mRNAs in rat glial cell cultures by Semax, an adrenocorticotropic hormone analogue, Neurosci. Lett. 308 (2001) (2) 115-118]. In this work, we examined the action of Semax on rapid changes of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) gene expression in vivo. Male Wistar rats were treated for 1h with Semax (50 microg/kg, single intranasal application) and neurotrophin gene expression in rat brain was analyzed by real-time polymerase chain reaction (PCR). It was revealed that an intranasal application of Semax increased the expression of both neurotrophin genes in rat hippocampus. Bdnf gene expression also increased in the brainstem and cerebellum. Ngf gene expression decreased in rat frontal cortex. Thus, Semax induces rapid, gene- and region-specific changes in neurotrophin gene expression in normal rat brain.
七肽Semax是N端促肾上腺皮质激素片段(4 - 10)(ACTH(4 - 10))的类似物,已被证明具有多种神经保护作用。有一些研究将这些作用与在神经元细胞培养中应用肽类药物时神经营养因子基因表达的增加联系起来[M.I. 沙德林娜、O.V. 多洛托夫、I.A. 格里文科夫、P.A. 斯洛明斯基、L.A. 安德烈耶娃、L.S. 伊诺泽姆采娃、S.A. 林博尔斯卡、N.F. 米亚索耶多夫,促肾上腺皮质激素类似物Semax对大鼠神经胶质细胞培养中神经营养因子mRNA的快速诱导,《神经科学快报》308 (2001) (2) 115 - 118]。在这项研究中,我们检测了Semax对体内神经生长因子(NGF)和脑源性神经营养因子(BDNF)基因表达快速变化的作用。雄性Wistar大鼠用Semax(50微克/千克,单次鼻内给药)处理1小时,然后通过实时聚合酶链反应(PCR)分析大鼠脑中神经营养因子基因的表达。结果显示,鼻内给予Semax可增加大鼠海马中两种神经营养因子基因的表达。脑干和小脑中BDNF基因表达也增加。大鼠额叶皮质中NGF基因表达下降。因此,Semax可诱导正常大鼠脑中神经营养因子基因表达的快速、基因和区域特异性变化。