Differentially Expressed Genes of the Slc6a Family as Markers of Altered Brain Neurotransmitter System Function in Pathological States in Mice

Abstract

The neuromolecular mechanisms forming behavioral pathology developing in male mice in response to repeated experience of aggression and mixed anxiety-depressive disorder due to chronic social stress were studied. These studies tested the suggestion that altered expression of genes of the Slc6a family, which encode monoamine, GABA, taurine, glycine, and other amino acid transporter proteins can be used as an indicator of changes in the operation of the neurotransmitter systems in five parts of the brain involved in the processes forming pathological forms of behavior. The transcriptomes of brain areas in control, aggressive, and depressive mice were sequenced at Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). The analysis results (RNA-Seq) identified different changes in the expression of the transporter genes the Slc6a family depending on brain area, behavioral pathology, and the functions of the protein encoded by the corresponding genes. In particular, increases in the expression of most GABAergic Slc6a genes were seen in the hypothalamus, hippocampus, and striatum in depressive mice and in the hypothalamus of aggressive males. The midbrain raphe nuclei and ventral tegmental area showed specific and opposite changes in the expression of the monoaminergic genes. These data lead to the conclusion that the altered expression of the Slc6a genes, encoding the corresponding transporters, may serve as a marker for changes in the functions of the neurotransmitter systems in pathological states.