TY - JOUR
T1 - Circuit-wide Transcriptional Profiling Reveals Brain Region-Specific Gene Networks Regulating Depression Susceptibility
AU - Bagot, Rosemary C C.
AU - Cates, Hannah M M.
AU - Purushothaman, Immanuel
AU - Lorsch, Zachary S S.
AU - Walker, Deena M M.
AU - Wang, Junshi
AU - Huang, Xiaojie
AU - Schlüter, Oliver M M.
AU - Maze, Ian
AU - Peña, Catherine J J.
AU - Heller, Elizabeth A A.
AU - Issler, Orna
AU - Wang, Minghui
AU - Song, Won min
AU - Stein, Jason L
AU - Liu, Xiaochuan
AU - Doyle, Marie A A.
AU - Scobie, Kimberly N N.
AU - Sun, Hao Sheng S.
AU - Neve, Rachael L L.
AU - Geschwind, Daniel
AU - Dong, Yan
AU - Shen, Li
AU - Zhang, Bin
AU - Nestler, Eric J J.
N1 - Funding Information:
This work was supported by P50 MH096890 and a Hope for Depression Research Foundation grant to E.J.N., a 2014 NARSAD Young Investigator Award 22713 from the Brain & Behavior Research Foundation to R.C.B., R01AG046170 from the NIH/National Institute on Aging to B.Z. and M.W., U01AI111598-01 from NIH/National Institute of Allergy and Infectious Diseases to B.Z. and W.S., and K99 MH10237 to J.L.S. We thank Erin S. Calipari for comments on the manuscript.
Publisher Copyright:
© 2016 Elsevier Inc.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery.
AB - Depression is a complex, heterogeneous disorder and a leading contributor to the global burden of disease. Most previous research has focused on individual brain regions and genes contributing to depression. However, emerging evidence in humans and animal models suggests that dysregulated circuit function and gene expression across multiple brain regions drive depressive phenotypes. Here, we performed RNA sequencing on four brain regions from control animals and those susceptible or resilient to chronic social defeat stress at multiple time points. We employed an integrative network biology approach to identify transcriptional networks and key driver genes that regulate susceptibility to depressive-like symptoms. Further, we validated in vivo several key drivers and their associated transcriptional networks that regulate depression susceptibility and confirmed their functional significance at the levels of gene transcription, synaptic regulation, and behavior. Our study reveals novel transcriptional networks that control stress susceptibility and offers fundamentally new leads for antidepressant drug discovery.
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U2 - 10.1016/j.neuron.2016.04.015
DO - 10.1016/j.neuron.2016.04.015
M3 - Article
C2 - 27181059
AN - SCOPUS:84966622155
SN - 0896-6273
VL - 90
SP - 969
EP - 983
JO - Neuron
JF - Neuron
IS - 5
ER -