Selank in rat frontal cortex: neurotransmission gene expression by real-time PCR, a published study summary

Summary

This summary describes a 2016 study in Frontiers in Pharmacology by Volkova and colleagues at the Institute of Molecular Genetics, Russian Academy of Sciences, with a 2017 cell-culture follow-up from the same group. The authors measured the expression of 84 genes involved in neurotransmission in the frontal cortex of rats one and three hours after the animals received the heptapeptide Selank or gamma-aminobutyric acid (GABA), each at 300 micrograms per kilogram, using real-time PCR. The 2017 paper repeated the gene panel in cultured IMR-32 cells exposed to Selank, GABA, or both.

Peptide

Name

Selank

Sequence

Thr-Lys-Pro-Arg-Pro-Gly-Pro

CAS

129954-34-3

Formula

C₃₃H₅₇N₁₁O₉, approximately 751.9 g/mol

Class

Synthetic heptapeptide; the tetrapeptide tuftsin (Thr-Lys-Pro-Arg) extended at the C-terminus with Pro-Gly-Pro.

Study design

Model system (Volkova 2016): laboratory rats. The full paper states the strain, sex, numbers per group and housing.

Groups: rats received Selank or GABA at 300 micrograms per kilogram of body mass; frontal cortex was collected one hour or three hours later and compared with control animals. The route is stated in the methods of the full paper.

Endpoints measured: expression of 84 genes involved in neurotransmission, including the major subunits of the GABA receptor, transporters, ion channels, and dopamine and serotonin receptors, by real-time PCR. Correlation between the expression changes produced by Selank and those produced by GABA was calculated.

Model system (Filatova 2017): the neuroblastoma cell line IMR-32 in culture, exposed to Selank alone, GABA alone, or Selank together with GABA, with the same 84-gene panel measured by quantitative PCR. The paper also includes an arm with a second reference substance that is not summarised here.

Companion paper (Kolomin 2014): mouse spleen, with C3, Casp1, Il2rg and Xcr1 mRNA measured by real-time PCR at several time points after a single intraperitoneal exposure to Selank or to its fragment Gly-Pro at 100 micrograms per kilogram.

Reported findings

Volkova and colleagues reported significant changes in the expression of 45 of the 84 genes one hour after the animals received Selank or GABA, and changes in 22 genes at three hours. A positive correlation was reported between the expression changes produced by Selank and those produced by GABA within the first hour. The authors concluded that Selank caused a number of alterations in the expression of neurotransmission genes and proposed that one of its possible molecular mechanisms is allosteric modulation of the GABAergic system.

Filatova and colleagues reported no changes in the mRNA levels of the 84 genes in IMR-32 cells exposed to Selank alone. When Selank and GABA were applied together, the expression changes produced by GABA alone were reported to be almost completely suppressed. The authors concluded that Selank has no direct effect on the mRNA levels of these genes in IMR-32 cells, and that the data are partially consistent with an effect on the interaction of GABA with GABA-A receptors.

Kolomin and colleagues reported a threefold decrease in C3 mRNA in mouse spleen 30 minutes after Selank, with a similar change after Gly-Pro, a wave-like change in Casp1 mRNA, early changes in Il2rg mRNA, and a reduction in Xcr1 mRNA at 90 minutes after either peptide.

The individual gene lists, fold changes and p-values are in the full papers and are not reproduced here.

Limitations

All three papers come from one research institute. The rat study reports gene expression at two time points only, and mRNA changes do not establish changes in protein or in function. The cell-culture work used a neuroblastoma line, which differs from primary neurons. No human data are summarised here.

References

1. Volkova A, Shadrina M, Kolomin T, Andreeva L, Limborska S, Myasoedov N, Slominsky P. Frontiers in Pharmacology. 2016;7:31. PMID 26924987. DOI 10.3389/fphar.2016.00031.
2. Filatova E, Kasian A, Kolomin T, et al. Frontiers in Pharmacology. 2017;8:89. PMID 28293190. DOI 10.3389/fphar.2017.00089.
3. Kolomin T, Morozova M, Volkova A, Shadrina M, Andreeva L, Slominsky P, Limborska S, Myasoedov N. Molecular Immunology. 2014;58(1):50-55. PMID 24291245. DOI 10.1016/j.molimm.2013.11.002.