Search bioRxiv⌕ Search

Biology subjects

Babenko, V. N.

Publications and source records attributed to Babenko, V. N..

5 recordsLinked to original sources

Neurotransmitter Genes in the Nucleus Accumbens that Are Involved in the Development of Behavioral Pathology After Positive Fighting Experiences and Their Deprivation. A Conceptual Paradigm for Neurogenomic Data Analysis

It has been shown earlier that repeated positive fighting experience in daily agonistic interactions is accompanied by the development of psychosis-like behavior with signs of an addiction-like state associated with changes in the expression of genes encoding the proteins involved in the main neurotransmitter events in some brain regions of aggressive male mice. Fighting deprivation (a no-fight period of 2 weeks) causes a significant increase in their aggressiveness. This paper is aimed at studying--after a period of fighting deprivation--the involvement of genes (associated with neurotransmitter systems within the nucleus accumbens) in the above phenomena. The nucleus accumbens is known to participate in reward-related mechanisms of aggression. We found the following differentially expressed genes (DEGs), whose expression significantly differed from that in controls and/or mice with positive fighting experience in daily agonistic interactions followed by fighting deprivation: catecholaminergic genes Th, Drd1, Drd2, Adra2c, Ppp1r1b, and Maoa; serotonergic genes Maoa, Htr1a, Htr1f, and Htr3a; opioidergic genes Oprk1, Pdyn, and Penk; and glutamatergic genes Grid1, Grik4, Grik5, Grin3a, Grm2, Grm5, Grm7, and Gad1. The expression of DEGs encoding proteins of the GABAergic system in experienced aggressive male mice mostly returned to control levels after fighting deprivation except for Gabra5. In light of the conceptual paradigm for analyzing data that was chosen in our study, the aforementioned DEGs associated with the behavioral pathology can be considered responsible for consequences of aggression followed by fighting deprivation, including mechanisms of an aggression relapse.

neuroscience↗

Snapper: a high-sensitive algorithm to detect methylation motifs based on Oxford Nanopore reads

The Oxford Nanopore technology has a great potential for the analysis of genome methylation, including full-genome methylome profiling. However, there are certain issues while identifying methylation motif sequences caused by low sensitivity of the currently available motif enrichment algorithms. Here, we present Snapper, a new highly-sensitive approach to extract methylation motif sequences based on a greedy motif selection algorithm. Snapper has shown higher enrichment sensitivity compared with the MEME tool coupled with Tombo or Nanodisco instruments, which was demonstrated on H. pylori strain J99 studied earlier using the PacBio technology. In addition, we used Snapper to characterize the total methylome of a new H.pylori strain A45. The analysis revealed the presence of at least 4 methylation sites that have not been described for H. pylori earlier. We experimentally confirmed a new CCAG-specific methyltransferase and indirectly inferred a new CCAAK-specific methyltransferase.

bioinformatics↗

Reduced Expression of Slc Genes in the VTA and NAcc of Male Mice with Positive Fighting Experience

There are many psychiatric medications targeting the activity of SLC transporters. Therefore, further research is needed to elucidate the expression profiles of the Slc* genes, which may serve as markers of altered brain metabolic processes and neurotransmitter activities in psychoneurological disorders. We studied differentially expressed Slc genes using the transcriptomic profiles in the ventral tegmental area (VTA), nucleus accumbens (NAcc), and prefrontal cortex (PFC) of male mice with psychosis-like behavior induced by repeated aggression experience in daily agonistic interactions which are accompanied by wins. Most of differentially expressed Slc genes in the VTA and NAcc (12 of 17 and 25 of 26, respectively) were downregulated, which was not the case in the PFC (6 and 5, up- and down, respectively). Also, the majority of these genes were shown to have brain region-specific expression profiles. In the VTA and NAcc altered expression was observed for the genes encoding the transporters of neurotransmitters as well as inorganic and organic ions, amino acids, metals, glucose, etc. This means alteration in transport functions for many substrates, which results in complete disruption of all cellular and neurotransmitter processes. The neurotransmitter systems, especially, the dopaminergic one, in male mice with positive fighting experience in daily agonistic interactions undergo changes leading to profound genomic modifications which include downregulated expression of the majority of the Slc* genes at least in the VTA and NAcc, which is attributable to chronic stimulation of the reward systems.

neuroscience↗

Aberrant expression of collagen family genes in the brain regions developing under agonistic interactions in male mice

As previously established, chronic agonistic interactions lead to the development of depression-like state under social defeat stress in the defeated mice and pathology of aggressive behavior in the winning mice. According to the numerous research data, these psychopathological states are accompanied by tremendous molecular and cellular changes in the brain. The paper aimed to study the influence of 20-day period of agonistic interactions on the expression mode of collagen family genes, encoding the proteins, which are basic components of extracellular matrix (ECM), in the different brain regions of mice using the RNA-Seq database. Most of the differentially expressed collagen genes were upregulated in the hypothalamus and striatum of chronically aggressive and defeated mice and in the hippocampus of the defeated mice. In the ventral tegmental area the most genes were downregulated in both experimental groups. It has been assumed that aberrant expression of collagen genes induced by long experience of agonistic interactions can indicate defects of ECM specific for brain regions in mice with alternative social experiences. This study first shows remodeling of molecular base in the ECM under development of experimental psychoneuropathologies.\n\nCorresponding authors: Kudryavtseva N.N., n.n.kudryavtseva@gmail.com; Babenko V.N., bob@bionet.nsc.ru

neuroscience↗

Abnormal Social Behaviors And Dysfunction Of Autism-Related Genes Associated With Daily Agonistic Interactions In Mice

BackgroundThe ability of people to communicate with each other is a necessary component of social behavior and the normal development of individuals who live in a community. An apparent decline in sociability may be the result of a negative social environment or the development of affective and neurological disorders, including autistic spectrum disorders. The behavior of these humans may be characterized by the deterioration of socialization, low communication, and repetitive and restricted behaviors. This study aimed to analyze changes in the social behaviors of male mice induced by daily agonistic interactions and investigate the involvement of genes, related with autistic spectrum disorders in the process of the impairment of social behaviors.\n\nMethodsAbnormal social behavior is induced by repeated experiences of aggression accompanied by wins (winners) or chronic social defeats (losers) in daily agonistic interactions in male mice. The collected brain regions (the midbrain raphe nuclei, ventral tegmental area, striatum, hippocampus, and hypothalamus) were sequenced at JSC Genoanalytica (http://genoanalytica.ru/, Moscow, Russia). The Cufflinks program was used to estimate the gene expression levels. Bioinformatic methods were used for the analysis of differentially expressed genes in male mice.\n\nResultsThe losers exhibited an avoidance of social contacts toward unfamiliar conspecific, immobility and low communication on neutral territory. The winners demonstrated aggression and hyperactivity in this condition. The exploratory activity (rearing) and approaching behavior time towards the partner were decreased, and the number of episodes of repetitive self-grooming behavior was increased in both social groups. These symptoms were similar to the symptoms observed in animal models of autistic spectrum disorders. In an analysis of the RNA-Seq database of the whole transcriptome in the brain regions of the winners and losers, we identified changes in the expression of the following genes, which are associated with autism in humans: Tph2, Maoa, Slc6a4, Htr7,Gabrb3, Nrxn1, Nrxn2, Nlgn1, Nlgn2, Nlgn3, Shank2, Shank3, Fmr1, Ube3a, Pten, Cntn3, Foxp2, Oxtr, Reln, Cadps2, Pcdh10, Ctnnd2, En2, Arx, Auts2, Mecp2, and Ptchd1.Common and specific changes in the expression of these genes in different brain regions were identified in the winners and losers.\n\nConclusionsThis research demonstrates for the first time that abnormalities in social behaviors that develop under a negative social environment in adults may be associated with alterations in expression of genes, related with autism in the brain.

neuroscience↗