Selank Administration Affects the Expression of Some Genes Involved in GABAergic

Clinical studies have shown the similarity of the spectrum of physiological effects of Selank and classical benzodiazepines, such as diazepam and phenazepam. These data suggest that there is a similar basis of their mechanism of action. To test this hypothesis we studied the effect of Selank and GABA on the expression of genes involved in neurotransmission. We analyzed the expression of 84 genes involved in neurotransmission (e.g., the major subunit of the GABA receptor, transporters, ion channels, dopamine, and serotonin receptors) in the frontal cortex of rats 1 and 3 h after the administration of Selank or GABA (300 μg/kg) using real-time PCR method. We found significant changes in the expression of 45 genes 1 h after the administration of the compounds. Three hours after Selank or GABA administration, 22 genes changed their expression. We found a positive correlation between the changes in genes expression within 1 h after administration of Selank or GABA. Our results showed that Selank caused a number of alterations in the expression of genes involved in neurotransmission. The data obtained indicate that Selank is characterized by its complex effects on nerve cells, and one of its possible molecular mechanisms is associated with allosteric modulation of the GABAergic system.

Regulatory peptides play key roles in the formation, development, and normal functioning of the nervous system. They are not understood fully despite the accumulating experimental data in recent years. The study of their mechanisms of action is of particular interest because regulatory peptides have potential in the creation of safe drugs on their basis with specific clinical properties and direct physiological effects. One representative of this class of drugs is the synthetic regulatory peptide Selank. It was designed and produced at the Institute of Molecular Genetics, Russian Academy of Sciences, in cooperation with the V.V. Zakusov Research Institute of Pharmacology, Russian Academy of Medical Sciences. Selank is a synthetic analog of the endogenous tuftsin molecule (the short Thr-Lys-Pro-Arg fragment of the human immunoglobulin G heavy chain), which was elongated at the C terminus via the addition of three natural L-amino acids (Pro-Gly-Pro) to improve its metabolic stability and yield a relatively longer duration (Ashmarin et al., 2005; Ashmarin, 2007).

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