Elevation of p11 in lateral habenula mediates depression-like behavior.

Molecular Psychiatry
J-S SeoPaul Greengard

Abstract

The lateral habenula (LHb) is a key brain region involved in the pathophysiology of depression. It is activated by stimuli associated with negative experiences and is involved in encoding aversive signals. Hyperactivity of LHb is found in both rodent models of depression and human patients with depression. However, little is known about the underlying molecular mechanisms. Here we show that in LHb neurons, p11, a multifunctional protein implicated in depression, is significantly upregulated by chronic restraint stress. Knockdown of p11 expression in LHb alleviates the stress-induced depression-like behaviors. Moreover, chronic restraint stress induces bursting action potentials in LHb neurons, which are abolished by p11 knockdown. Overexpression of p11 in dopamine D2 receptor-containing LHb neurons of control mice induces depression-like behaviors. These results have identified p11 in LHb as a key molecular determinant regulating negative emotions, which may help to understand the molecular and cellular basis of depression.

References

Mar 22, 2001·Biochemistry·M RuseR L Eckert
Nov 24, 2004·Nature Neuroscience·Ziv M WilliamsEmad N Eskandar
May 14, 2005·Nature Reviews. Neuroscience·E Ron de KloetFlorian Holsboer
Sep 20, 2005·The Journal of Biological Chemistry·Emmanuelle DonierJohn N Wood
Jan 10, 2006·Science·Per SvenningssonPaul Greengard
Nov 7, 2006·Current Opinion in Pharmacology·Per Svenningsson, Paul Greengard
May 15, 2007·Medical Hypotheses·Alexander Sartorius, Fritz A Henn
May 25, 2007·Nature·Masayuki Matsumoto, Okihide Hikosaka
Sep 14, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Christopher Pittenger, Ronald S Duman
Apr 3, 2008·The European Journal of Neuroscience·Lucas LecourtierBita Moghaddam
Oct 17, 2008·Nature·Vaishnav Krishnan, Eric J Nestler
Dec 2, 2008·Nature Neuroscience·Masayuki Matsumoto, Okihide Hikosaka
Feb 13, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jennifer L Warner-SchmidtPaul Greengard
Apr 3, 2009·The Journal of Clinical Investigation·Helen S Mayberg
Oct 23, 2009·Biological Psychiatry·Alexander SartoriusAndreas Meyer-Lindenberg
Jun 19, 2010·Nature Reviews. Neuroscience·Okihide Hikosaka
Jun 16, 2012·The Journal of Comparative Neurology·Hidenori AizawaHitoshi Okamoto
Jun 26, 2012·Nature Neuroscience·Alice M Stamatakis, Garret D Stuber
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Jennifer L Warner-SchmidtPaul Greengard
Jul 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ji-Seon SeoPyung-Lim Han
Oct 16, 2012·Nature·Stephan LammelRobert C Malenka
Apr 26, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Thomas C JhouSatoshi Ikemoto
Sep 5, 2013·Nature Reviews. Neuroscience·Per SvenningssonPaul Greengard
Aug 27, 2014·Nature Neuroscience·Christophe D ProulxRoberto Malinow
Sep 26, 2015·Nature Neuroscience·Bruce S McEwenCarla Nasca
Jan 14, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alice M StamatakisGarret D Stuber
Dec 3, 2016·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Phillip M BakerAleksandra Vicentic

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Citations

Aug 8, 2018·Frontiers in Neuroscience·Alvaro Nuno-PerezSalvatore Lecca
Feb 6, 2019·Cold Spring Harbor Symposia on Quantitative Biology·Yihui CuiHailan Hu
Jun 4, 2019·Proceedings of the National Academy of Sciences of the United States of America·Steven J ShabelRoberto Malinow
Apr 10, 2020·Nature Reviews. Neuroscience·Hailan HuYan Yang
Dec 26, 2018·Frontiers in Synaptic Neuroscience·Caroline A BrowneIrwin Lucki
Jun 25, 2019·Frontiers in Psychiatry·Philip W Gold, Bashkim Kadriu
Sep 11, 2020·International Journal of Molecular Sciences·Matas Vitkauskas, Ajay S Mathuru
Oct 27, 2020·Frontiers in Psychiatry·Zhenghao Duan, Jie Lu
May 19, 2020·Trends in Pharmacological Sciences·Ji-Seon Seo, Per Svenningsson
Jul 9, 2021·Molecular Psychiatry·Ji-Seon SeoPaul Greengard
Nov 16, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Woonhee Kim, ChiHye Chung

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

PRISM
GraphPad

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