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The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression
Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in the expression of long noncoding RNAs (lncRNAs), a class of regulatory transcripts, in human postmortem brain tissue that are pro...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710883/ https://www.ncbi.nlm.nih.gov/pubmed/36449610 http://dx.doi.org/10.1126/sciadv.abn9494 |
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author | Issler, Orna van der Zee, Yentl Y. Ramakrishnan, Aarthi Xia, Sunhui Zinsmaier, Alexander K. Tan, Chunfeng Li, Wei Browne, Caleb J. Walker, Deena M. Salery, Marine Torres-Berrío, Angélica Futamura, Rita Duffy, Julia E. Labonte, Benoit Girgenti, Matthew J. Tamminga, Carol A. Dupree, Jeffrey L. Dong, Yan Murrough, James W. Shen, Li Nestler, Eric J. |
author_facet | Issler, Orna van der Zee, Yentl Y. Ramakrishnan, Aarthi Xia, Sunhui Zinsmaier, Alexander K. Tan, Chunfeng Li, Wei Browne, Caleb J. Walker, Deena M. Salery, Marine Torres-Berrío, Angélica Futamura, Rita Duffy, Julia E. Labonte, Benoit Girgenti, Matthew J. Tamminga, Carol A. Dupree, Jeffrey L. Dong, Yan Murrough, James W. Shen, Li Nestler, Eric J. |
author_sort | Issler, Orna |
collection | PubMed |
description | Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in the expression of long noncoding RNAs (lncRNAs), a class of regulatory transcripts, in human postmortem brain tissue that are profoundly lost in depression. One such human lncRNA, RP11-298D21.1 (which we termed FEDORA), is enriched in oligodendrocytes and neurons and up-regulated in the prefrontal cortex (PFC) of depressed females only. We found that virally expressing FEDORA selectively either in neurons or in oligodendrocytes of PFC promoted depression-like behavioral abnormalities in female mice only, changes associated with cell type–specific regulation of synaptic properties, myelin thickness, and gene expression. We also found that blood FEDORA levels have diagnostic implications for depressed women and are associated with clinical response to ketamine. These findings demonstrate the important role played by lncRNAs, and FEDORA in particular, in shaping the sex-specific landscape of the brain and contributing to sex differences in depression. |
format | Online Article Text |
id | pubmed-9710883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97108832022-12-07 The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression Issler, Orna van der Zee, Yentl Y. Ramakrishnan, Aarthi Xia, Sunhui Zinsmaier, Alexander K. Tan, Chunfeng Li, Wei Browne, Caleb J. Walker, Deena M. Salery, Marine Torres-Berrío, Angélica Futamura, Rita Duffy, Julia E. Labonte, Benoit Girgenti, Matthew J. Tamminga, Carol A. Dupree, Jeffrey L. Dong, Yan Murrough, James W. Shen, Li Nestler, Eric J. Sci Adv Biomedicine and Life Sciences Women suffer from depression at twice the rate of men, but the underlying molecular mechanisms are poorly understood. Here, we identify marked baseline sex differences in the expression of long noncoding RNAs (lncRNAs), a class of regulatory transcripts, in human postmortem brain tissue that are profoundly lost in depression. One such human lncRNA, RP11-298D21.1 (which we termed FEDORA), is enriched in oligodendrocytes and neurons and up-regulated in the prefrontal cortex (PFC) of depressed females only. We found that virally expressing FEDORA selectively either in neurons or in oligodendrocytes of PFC promoted depression-like behavioral abnormalities in female mice only, changes associated with cell type–specific regulation of synaptic properties, myelin thickness, and gene expression. We also found that blood FEDORA levels have diagnostic implications for depressed women and are associated with clinical response to ketamine. These findings demonstrate the important role played by lncRNAs, and FEDORA in particular, in shaping the sex-specific landscape of the brain and contributing to sex differences in depression. American Association for the Advancement of Science 2022-11-30 /pmc/articles/PMC9710883/ /pubmed/36449610 http://dx.doi.org/10.1126/sciadv.abn9494 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Issler, Orna van der Zee, Yentl Y. Ramakrishnan, Aarthi Xia, Sunhui Zinsmaier, Alexander K. Tan, Chunfeng Li, Wei Browne, Caleb J. Walker, Deena M. Salery, Marine Torres-Berrío, Angélica Futamura, Rita Duffy, Julia E. Labonte, Benoit Girgenti, Matthew J. Tamminga, Carol A. Dupree, Jeffrey L. Dong, Yan Murrough, James W. Shen, Li Nestler, Eric J. The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title | The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title_full | The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title_fullStr | The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title_full_unstemmed | The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title_short | The long noncoding RNA FEDORA is a cell type– and sex-specific regulator of depression |
title_sort | long noncoding rna fedora is a cell type– and sex-specific regulator of depression |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710883/ https://www.ncbi.nlm.nih.gov/pubmed/36449610 http://dx.doi.org/10.1126/sciadv.abn9494 |
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