Selank has the same anti-anxiety effect as classical benzodiazepines

1. Selank has the same anti-anxiety effect as classical benzodiazepines Clinical studies have shown that Selank has the same anti-anxiety effect as classical benzodiazepines, and can enhance the inhibition of GABA by allosteric regulation of GABAA receptor. These data indicate that the molecular mechanism of Selank effect may also be related to its ability to affect the performance of gaba energy system. In order to verify this hypothesis, we used qPCR method to study the expression changes of 84 genes involved in the function of gaba-ergic system and neurotransmission during the culture of neuroblastoma IMR-32 cells. As a test substance, in addition to Selank, we also selected the main GABAA receptor ligand GABA, atypical antipsychotics, olanzapine, and combinations of these compounds (Selank and GABA; Selank and olanzapine). We found that the mRNA level of the studied gene did not change under the action of Selank. The combined action of GABA and Selank almost completely inhibited the gene expression changes of mRNA level changes under the action of GABA. When Selank was used in combination with olanzapine, more gene expression changes were observed compared with olanzapine alone. The data obtained showed that Selank had no direct effect on the mRNA level of gabaergic system gene in neuroblastoma IMR-32 cells. At the same time, our research results partially confirmed the hypothesis that peptides might affect the interaction between GABA and GABAA receptor. Our data also show that Selank may enhance the effect of olanzapine on the expression of the studied genes. Recent studies have shown that the number of specific binding ligands ([3H] GABA) will change in the presence of Selank, and the initial intranasal administration of Selank will lead to changes in the number of specific binding sites of GABA, but will not affect the receptor affinity (V'yunova et al., 2014). Based on these data, the author believes that Selank can lead to rapid changes in the state of GABAergic system by binding to GABAA receptor and allosterically regulating the activity of GABAA receptor. The transcriptome changes we found earlier may be partially realized by Selank's regulation of GABAA receptor activity. Previously, we also found that there was a positive correlation between the expression of neurotransmission related genes in the frontal cortex of rats within 1 hour after the administration of Selank or GABA. Our research results show that Selank causes many changes in the function of gaba-ergic system and gene expression in the process of neurotransmission (Volkova et al., 2016). In order to verify the hypothesis that Selank may have an effect by regulating the activity of GABAA receptor, we studied the expression changes of 84 genes involved in neurotransmission in Selank reaction in IMR-32 cell line. The human neuroblastoma cell line IMR-32 was selected for research because these cells expressed functional GABAA receptors (Anderson et al., 1993; Noble et al., 1993; Sapp and Ye, 2000). In order to detect the effects related to the action of GABAA receptor, we also analyzed the response changes of GABA (a major GABAA receptor ligand) and olanzapine (an atypical benzodiazepine with the most obvious affinity for 5-HT2 receptor) to gene expression (Bymaster et al., 1996).

2. Selank had no direct effect on the expression of gabaergic system gene in neuroblastoma IMR-32 cells. We can assume that the difference in the expression profile of GABA after mixed incubation with Selank and GABA partially confirms the hypothesis that peptides may affect the interaction between GABA and GABAA receptor.