title: GABA, Selank, and Olanzapine Affect the Expression of Genes Involved in GABAergic Neurotransmission in IMR-32 Cells.
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 GABAAreceptors. 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 GABAAreceptor 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 GABAAreceptors. Our data also suggest that Selank may enhance the effect of olanzapine on the expression of the genes studied.
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Elena
authors.initials: E
authors.lastname: Filatova
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Anastasiya
authors.initials: A
authors.lastname: Kasian
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Timur
authors.initials: T
authors.lastname: Kolomin
authors.affiliation: Laboratory of Tumor Cells Genetics, Blokhin Russian Cancer Research Center, Ministry of Health of the Russian Federation Moscow, Russia.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Rybalkina
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Anelya
authors.initials: A
authors.lastname: Alieva
authors.affiliation: Department of Chemistry of Physiologically Active Compounds, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Lyudmila
authors.initials: L
authors.lastname: Andreeva
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Limborska
authors.affiliation: Department of Chemistry of Physiologically Active Compounds, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Myasoedov
authors.affiliation: Group of Neurogenetics and Developmental Genetics, Institute of Gene Biology, Russian Academy of Sciences Moscow, Russia.
authors.forename: Galina
authors.initials: G
authors.lastname: Pavlova
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Petr
authors.initials: P
authors.lastname: Slominsky
authors.affiliation: Department of Molecular Basis of Human Genetics, Institute of Molecular Genetics, Russian Academy of Sciences Moscow, Russia.
authors.forename: Maria
authors.initials: M
authors.lastname: Shadrina
keywords: GABA; IMR-32 cells; Selank; gene expression; olanzapine