GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells

Elena Filatova; Anastasiya Kasian; Timur Kolomin; Ekaterina Rybalkina; Anelya Alieva; Lyudmila Andreeva; Svetlana Limborska; Nikolay Myasoedov; Galina Pavlova; Petr Slominsky; Maria Shadrina

doi:10.3389/fphar.2017.00089

GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells

Front Pharmacol. 2017 Feb 28:8:89. doi: 10.3389/fphar.2017.00089. eCollection 2017.

Affiliations

¹ Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
² Laboratory of Tumor Cells Genetics, Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation Moscow, Russia.
³ Department of Chemistry of Physiologically Active Compounds, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
⁴ Group of Neurogenetics and Developmental Genetics, Institute of Gene Biology, Russian Academy of Sciences Moscow, Russia.

Abstract

Clinical studies have shown that Selank had an anxiolytic effect comparable to that of classical benzodiazepine drugs, which can enhance the inhibitory effect of GABA by allosteric modulation of GABA_A receptors. These data suggest that the molecular mechanism of the effect of Selank may also be related to its ability to affect the performance of the GABAergic system. To test this hypothesis, we studied the changes in expression of 84 genes involved in the functioning of the GABAergic system and in the processes of neurotransmission in the culture of neuroblastoma IMR-32 cells using qPCR method. As test substances, in addition to Selank, we selected the major GABA_A receptor ligand, GABA, the atypical antipsychotic, olanzapine, and combinations of these compounds (Selank and GABA; Selank and olanzapine). We found no changes in the mRNA levels of the genes studied under the effect of Selank. The combined effect of GABA and Selank led to nearly complete suppression of changes in expression of genes in which mRNA levels changed under the effect of GABA. When Selank was used in conjunction with olanzapine, the expression alterations of more genes were observed compared with olanzapine alone. The data obtained indicate that Selank has no direct effect on the mRNA levels of the GABAergic system genes in neuroblastoma IMR-32 cells. At the same time, our results partially confirm the hypothesis that the peptide may affect the interaction of GABA with GABA_A receptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied.

Keywords: GABA; IMR-32 cells; Selank; gene expression; olanzapine.