Babenko, V. N. | Search bioRxiv

bioRxiv2018

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↗

bioRxiv2017

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↗