Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus
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 diso...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-01-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00454/full |
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| author | Chaoqun Li Feifei Cao Shengli Li Shenglin Huang Wei Li Nashat Abumaria Nashat Abumaria |
| author_facet | Chaoqun Li Feifei Cao Shengli Li Shenglin Huang Wei Li Nashat Abumaria Nashat Abumaria |
| author_sort | Chaoqun Li |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-20T17:43:46Z |
| format | Article |
| id | doaj.art-ceaf904bb90a4293a9038dceb7779881 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-20T17:43:46Z |
| publishDate | 2018-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-ceaf904bb90a4293a9038dceb77798812022-12-21T19:31:03ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992018-01-011010.3389/fnmol.2017.00454331575Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse HippocampusChaoqun Li0Feifei Cao1Shengli Li2Shenglin Huang3Wei Li4Nashat Abumaria5Nashat Abumaria6Institutes of Brain Science, Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitutes of Brain Science, Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitutes of Brain Science, Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitutes of Brain Science, Collaborative Innovation Center for Brain Science, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Laboratory Animal Science, Shanghai Medical College, Fudan University, Shanghai, ChinaAlthough 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.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00454/fullhippocampuslearned helplessnesslncRNAsRNA-seqsynapse |
| spellingShingle | Chaoqun Li Feifei Cao Shengli Li Shenglin Huang Wei Li Nashat Abumaria Nashat Abumaria Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus Frontiers in Molecular Neuroscience hippocampus learned helplessness lncRNAs RNA-seq synapse |
| title | Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus |
| title_full | Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus |
| title_fullStr | Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus |
| title_full_unstemmed | Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus |
| title_short | Profiling and Co-expression Network Analysis of Learned Helplessness Regulated mRNAs and lncRNAs in the Mouse Hippocampus |
| title_sort | profiling and co expression network analysis of learned helplessness regulated mrnas and lncrnas in the mouse hippocampus |
| topic | hippocampus learned helplessness lncRNAs RNA-seq synapse |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00454/full |
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