Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia

Abstract

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.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

pMCAO:

Permanent middle cerebral artery occlusion

Bdnf:

Brain-derived neurotropic factor

Ngf:

Nerve growth factor

Gapdh:

Glyceraldehyde-3-phosphate dehydrogenase

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Acknowledgments

This study was supported by the Russian Foundation for Basic Research (project no. 08-04-01279), Molecular and Cell Biology program of the Russian Academy of Sciences, and the Federal Support of Leading Schools of the Russian Ministry of Science and Education.

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Correspondence to Veronika G. Dmitrieva.

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Dmitrieva, V.G., Povarova, O.V., Skvortsova, V.I. et al. Semax and Pro-Gly-Pro Activate the Transcription of Neurotrophins and Their Receptor Genes after Cerebral Ischemia. Cell Mol Neurobiol 30, 71–79 (2010). https://doi.org/10.1007/s10571-009-9432-0

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Keywords

  • Neurotrophin
  • Trk receptor
  • Semax
  • PGP
  • Cerebral ischemia