Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

Abstract

Chronic social defeat stress leads to the development of anxiety- and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. Most Rps, Rpl, Mprs, and Mprl genes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with “ribosomopathies.”

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

“…Interestingly, all of the ribosomal and mitoribosomal genes were upregulated in the winners in this region [Smagin et al 2016b] and most of them were downregulated in the losers [Smagin et al 2016a]. These dynamics in changes of expression of Rp* genes we connected with different cell proliferation in this brain region.…”

“…The upregulation of most Col* genes in the hypothalamus of the winners and losers may be the response to the chronic social stress inducing development of anxiety in both participants of social conflicts [Kudryavtseva & Avgustinovich 1998; Kudryavtseva et al [Smagin et al 2016a;Smagin et al 2016b]. It's therefore natural to suppose the coexpression or joint expression elevation of numerous genes developing under chronic social stress of agonistic interactions.…”

“…We can assume the dysfunction of the ECM due to aberrant Col* gene expression. We can suppose also that changed neurotransmitter activity involved in the regulation of pathological states primarily creates the conditions for development of aberrant functioning of the ECM which, as consequence, produces changes in works of many metabolic genes including ribosomal and mitoribosomal genes shown earlier for brain regions [Smagin et al 2016a;Smagin et al 2016b].…”

“…It was established that under chronic social defeat stress the adult brain undergoes numerous molecular and cellular changes [Kudryavtseva et al 2004;Berton et al 2006;Boyarskikh et al 2013]. Analyzing the whole transcriptome in brain of depressive mice, we have found changes in the expression of serotonergic [Smagin et al 2013;, dopaminergic [Kovalenko et al 2016], glutamatergic and GABAergic ] genes as well as ribosomal and mitoribosomal genes [Smagin et al 2016a;Smagin et al 2016b] in different brain regions. Changes in DNA methylation, histone acetylation and chromatin remodeling often accompany these changes [Hollis et al 2010;Kenworthy et al 2014], as well as decreases in hippocampal neurogenesis rates [Ferragud et al 2010;Lagace et al 2010;Van Bokhoven et al 2011] in defeated mice.…”

“…We used the methods described earlier [Smagin et al 2016a;Smagin et al 2016b]. The collected samples were sequenced at JSC Genoanalytica (www.genoanalytica.ru, Moscow, Russia), and the mRNA was extracted using a Dynabeads mRNA Purification Kit (Ambion, Thermo Fisher Scientific, Waltham, MA, USA).…”