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Elevation of p11 in lateral habenula mediates depression-like behavior.
Seo, J-S; Zhong, P; Liu, A; Yan, Z; Greengard, P.
Affiliation
  • Seo JS; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
  • Zhong P; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USA.
  • Liu A; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USA.
  • Yan Z; Department of Physiology and Biophysics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo, NY, USA.
  • Greengard P; Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, New York, NY, USA.
Mol Psychiatry ; 23(5): 1113-1119, 2018 05.
Article de En | MEDLINE | ID: mdl-28507317
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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéines S100 / Annexine A2 / Habénula / Dépression Limites: Animals Langue: En Journal: Mol Psychiatry Sujet du journal: BIOLOGIA MOLECULAR / PSIQUIATRIA Année: 2018 Type de document: Article Pays d'affiliation: États-Unis d'Amérique

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Protéines S100 / Annexine A2 / Habénula / Dépression Limites: Animals Langue: En Journal: Mol Psychiatry Sujet du journal: BIOLOGIA MOLECULAR / PSIQUIATRIA Année: 2018 Type de document: Article Pays d'affiliation: États-Unis d'Amérique