Sex-Specific Role for the Long Non-coding RNA LINC00473 in Depression

被引：105

作者：

Issler, Orna ^{[1
,2
]}

van der Zee, Yentl Y. ^{[1
,2
,3
]}

Ramakrishnan, Aarthi ^{[1
,2
]}

Wang, Junshi ^{[4
]}

Tan, Chunfeng ^{[5
]}

Loh, Yong-Hwee E. ^{[1
,2
,8
]}

Purushothaman, Immanuel ^{[1
,2
]}

Walker, Deena M. ^{[1
,2
,9
]}

Lorsch, Zachary S. ^{[1
,2
]}

Hamilton, Peter J. ^{[1
,2
,10
]}

Pena, Catherine J. ^{[1
,2
,11
]}

Flaherty, Erin ^{[1
,2
,12
]}

Hartley, Brigham J. ^{[1
,2
,13
]}

Torres-Berrio, Angelica ^{[1
,2
]}

Parise, Eric M. ^{[1
,2
]}

Kronman, Hope ^{[1
,2
]}

Duffy, Julia E. ^{[1
,2
]}

Estill, Molly S. ^{[1
,2
]}

Calipari, Erin S. ^{[1
,2
,14
]}

Labonte, Benoit ^{[1
,2
,15
]}

Neve, Rachael L. ^{[6
]}

Tamminga, Carol A. ^{[5
]}

Brennand, Kristen J. ^{[1
,2
,7
]}

Dong, Yan ^{[4
]}

Shen, Li ^{[1
,2
]}

Nestler, Eric J. ^{[1
,2
]}

机构：

[1] Icahn Sch Med Mt Sinai, Nash Family Dept Neurosci, New York, NY 10029 USA

[2] Icahn Sch Med Mt Sinai, Friedman Brain Inst, New York, NY 10029 USA

[3] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, NL-6229 ER Maastricht, Netherlands

[4] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA

[5] Univ Texas Southwestern Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA

[6] Massachusetts Gen Hosp, Gene Delivery Technol Core, Cambridge, MA 02139 USA

[7] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Pamela Sklar Div Psychiat Genom, New York, NY 10029 USA

[8] Univ Southern Calif, USC Lib Bioinformat Serv, Los Angeles, CA 90007 USA

[9] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA

[10] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA USA

[11] Princeton Univ, Neurosci Inst, Princeton, NJ 08544 USA

[12] Columbia Univ, Zuckerman Inst, New York, NY USA

[13] New York Stem Cell Fdn, New York, NY USA

[14] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA

[15] Univ Laval, CERVO Brain Res Ctr, Dept Psychiat & Neurosci, Quebec City, PQ, Canada

来源：

NEURON | 2020年 / 106卷 / 06期

关键词：

PREFRONTAL CORTEX; UNIQUE FEATURES; SOCIAL DEFEAT; GENOME-WIDE; STRESS; CELLS; EVOLUTION; SUSCEPTIBILITY; TRANSCRIPTION; LOCALIZATION;

D O I：

10.1016/j.neuron.2020.03.023

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Depression is a common disorder that affects women at twice the rate of men. Here, we report that long non-coding RNAs (lncRNAs), a recently discovered class of regulatory transcripts, represent about one-third of the differentially expressed genes in the brains of depressed humans and display complex region- and sex-specific patterns of regulation. We identified the primate-specific, neuronal-enriched gene LINC00473 as downregulated in prefrontal cortex (PFC) of depressed females but not males. Using viral-mediated gene transfer to express LINC00473 in adult mouse PFC neurons, we mirrored the human sex-specific phenotype by inducing stress resilience solely in female mice. This sex-specific phenotype was accompanied by changes in synaptic function and gene expression selectively in female mice and, along with studies of human neuron-like cells in culture, implicates LINC00473 as a CREB effector Together, our studies identify LINC00473 as a female-specific driver of stress resilience that is aberrant in female depression.

引用

页码：912 / +

页数：20

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