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Semax-Induced Changes in Growth Factor mRNA Levels in the Rat Brain on the Third Day After Ischemia

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Abstract

The peptide Semax effectively protects brain tissues against ischemic stroke. However, the molecular mechanisms that underlie its action remain unknown. We used the focal cerebral ischemia rat model with permanent middle cerebral artery occlusion (pMCAO). During the experiments, animals were given intraperitoneal injections of Semax, Pro-Gly-Pro, or saline. We studied the effect of the peptides on the expression of more than 80 growth factor genes in the cortex. As a response to Semax administration, alterations in the expression of growth factor genes were detected at 3, 24, and 72 h after pMCAO. The most pronounced effects of Semax, i.e., the downregulation of the transcripts of 20 genes and the upregulation of 12 growth factor genes, were observed 3 days after artery occlusion. According to our data, Semax promoted the upregulation (by ≥10-fold) of the Csf3 and Artn genes, as well as of the cytokine genes Il1b and Il6. The peptide products of these genes have regulatory properties and exert neuroprotective effects in injured brain tissues. We presume that Semax triggers neuroprotective mechanisms by affecting these systems via the regulation of the expression of growth factor genes.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

PGP:

Tripeptide Pro-Gly-Pro

MCA:

Middle cerebral artery

pMCAO:

Permanent left middle cerebral artery occlusion

CNS:

Central nervous system

VEGF:

Vascular endothelial growth factor

PCR:

Polymerase chain reaction

REST:

Relative expression software tool

Th1 and Th2:

Type 1 and 2 helper T-cells

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Acknowledgements

This study was funded by the Russian Foundation for Basic Research (Grant Numbers 14-04-00487, 13-04-40083-H), the Program of the Russian Academy of Sciences “Molecular and Cellular Biology”, the Program “Support to Scientific Schools”, and a Grant of the President of the Russian Federation for federal support to young researchers, Candidates of Sciences, of Russia (Grant Number MК-2959.2014.4).

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Authors and Affiliations

  1. Human Molecular Genetics Department, Institute of Molecular Genetics, Russian Academy of Sciences, Kurchatov sq., 2, Moscow, Russia, 123182

    Ekaterina V. Medvedeva, Veronika G. Dmitrieva, Vasily V. Stavchansky, Svetlana A. Limborska, Nikolay F. Myasoedov & Lyudmila V. Dergunova

  2. Ministry of Health, Research Institute of Cerebrovascular Pathology and Stroke, Pirogov Russian National Research Medical University, Moscow, Russia, 117997

    Svetlana A. Limborska & Lyudmila V. Dergunova

  3. Department of Fundamental Medicine, Moscow State University, Moscow, Russia, 119192

    Oksana V. Povarova

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  1. Ekaterina V. Medvedeva
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  2. Veronika G. Dmitrieva
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  3. Vasily V. Stavchansky
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  6. Nikolay F. Myasoedov
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  7. Lyudmila V. Dergunova
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Correspondence to Ekaterina V. Medvedeva.

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Authors E. V. Medvedeva, V. G. Dmitrieva, V. V. Stavchansky, O. V. Povarova, S. A. Limborska, N. F. Myasoedov and L. V. Dergunova declare that they have no conflict of interest.

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All experimental protocols were approved by Bioethics Comission of Lomonosov Moscow State University in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publ. No. 80–23, revised 1996). This article does not contain any studies with human participants performed by any of the authors.

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Medvedeva, E.V., Dmitrieva, V.G., Stavchansky, V.V. et al. Semax-Induced Changes in Growth Factor mRNA Levels in the Rat Brain on the Third Day After Ischemia. Int J Pept Res Ther 22, 197–209 (2016). https://doi.org/10.1007/s10989-015-9498-0

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