Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Polter, A.
  • Beurel, E.
  • Yang, S. F.
  • Garner, R.
  • Song, L.
  • Miller, Courtney
  • Sweatt, J. D.
  • McMahon, L.
  • Bartolucci, A. A.
  • Li, X. H.
  • Jope, R. S.

publication date

  • July 2010

journal

  • Neuropsychopharmacology  Journal

abstract

  • Bipolar disorder, characterized by extreme manic and depressive moods, is a prevalent debilitating disease of unknown etiology. Because mood stabilizers, antipsychotics, antidepressants, and mood-regulating neuromodulators increase the inhibitory serine-phosphorylation of glycogen synthase kinase-3 (GSK3), we hypothesized that deficient GSK3 serine-phosphorylation may increase vulnerability to mood-related behavioral disturbances. This was tested by measuring behavioral characteristics of GSK3 alpha/beta(21A/21A/9A/9A) knockin mice with serine-to-alanine mutations to block inhibitory serine-phosphorylation of GSK3. GSK3 knockin mice displayed increased susceptibility to amphetamine-induced hyperactivity and to stress-induced depressive-like behaviors. Furthermore, serine-phosphorylation of GSK3 was reduced during both mood-related behavioral responses in wild-type mouse brain and in blood cells from patients with bipolar disorder. Therefore, proper control of GSK3 by serine-phosphorylation, which is targeted by agents therapeutic for bipolar disorder, is an important mechanism that regulates mood stabilization, and mice with disabled GSK3 serine-phosphorylation may provide a valuable model to study bipolar disorder.

subject areas

  • Adult
  • Aged
  • Animals
  • Behavior, Animal
  • Conditioning (Psychology)
  • Disease Models, Animal
  • Electroshock
  • Enzyme-Linked Immunosorbent Assay
  • Exploratory Behavior
  • Fear
  • Female
  • Glycogen Synthase Kinase 3
  • Helplessness, Learned
  • Hippocampus
  • Humans
  • In Vitro Techniques
  • Long-Term Potentiation
  • Male
  • Maze Learning
  • Mice
  • Mice, Knockout
  • Middle Aged
  • Mood Disorders
  • Pain
  • Pain Threshold
  • Phosphorylation
  • Serine
  • Swimming
scroll to property group menus

Research

keywords

  • amphetamine
  • bipolar disorder
  • depression
  • glycogen synthase kinase-3
  • lithium
scroll to property group menus

Identity

PubMed Central ID

  • PMC2891528

International Standard Serial Number (ISSN)

  • 0893-133X

Digital Object Identifier (DOI)

  • 10.1038/npp.2010.43

PubMed ID

  • 20357757
scroll to property group menus

Additional Document Info

start page

  • 1761

end page

  • 1774

volume

  • 35

issue

  • 8

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support