Abstract
Although studies provide insights into the neurobiology of stress and depression, the exact molecular mechanisms underlying their pathologies remain largely unknown. Long non-coding RNA (lncRNA) has been implicated in brain functions and behavior. A potential link between lncRNA and psychiatric disorders has been proposed. However, it remains undetermined whether IncRNA regulation, in the brain, contributes to stress or depression pathologies. In this study, we used a valid animal model of depression-like symptoms; namely learned helplessness, RNA-seq, Gene Ontology and co-expression network analyses to profile the expression pattern of lncRNA and mRNA in the hippocampus of mice. We identified 6346 differentially expressed transcripts. Among them, 340 lncRNAs and 3559 protein coding mRNAs were differentially expressed in helpless mice in comparison with control and/or non-helpless mice (inescapable stress resilient mice). Gene Ontology and pathway enrichment analyses indicated that induction of helplessness altered expression of mRNAs enriched in fundamental biological functions implicated in stress/depression neurobiology such as synaptic, metabolic, cell survival and proliferation, developmental and chromatin modification functions. To explore the possible regulatory roles of the altered lncRNAs, we constructed co-expression networks composed of the lncRNAs and mRNAs. Among our differentially expressed lncRNAs, 17% showed significant correlation with genes. Functional co-expression analysis linked the identified lncRNAs to several cellular mechanisms implicated in stress/depression neurobiology. Importantly, 57% of the identified regulatory lncRNAs significantly correlated with 18 different synapse-related functions. Thus, the current study identifies for the first time distinct groups of lncRNAs regulated by induction of learned helplessness in the mouse brain. Our results suggest that lncRNA-directed regulatory mechanisms might contribute to stress-induced pathologies; in particular, to inescapable stress-induced synaptic modifications.
Highlights
Depression is among the most devastating mental disorders
Using RNA-seq, we demonstrate that induction of helplessness, by exposure to inescapable stress, can misregulate mRNA expression, and Long non-coding RNA (lncRNA) expression in the mouse brain
Functional co-expression analysis predicts that some of the differentially expressed lncRNAs might play regulatory roles in several mechanisms previously implicated in stress/depression pathologies
Summary
Depression is among the most devastating mental disorders. The mechanisms underlying its pathologies remain to be elucidated. Numerous classes of non-coding RNAs including small non-coding RNAs such as miRNA and long non-coding RNAs (lncRNAs) such as natural antisense transcripts and long intergenic RNAs are emerging as major regulatory factors in several biological functions/dysfunctions (Faghihi and Wahlestedt, 2009; Barry and Mattick, 2012; Sauvageau et al, 2013; Kocerha et al, 2015; Huang et al, 2017) Such advances resulted in a paradigm shift in our thinking of the mechanisms underlying stress and/or depression disorders (Kocerha et al, 2015). Pharmacological studies show that regulation of miRNAs expression might
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
