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

Abigail Polter, Eleonore Beurel, Sufen Yang, Rakesha Garner, Ling Song, Courtney A. Miller, J. David Sweatt, Lori McMahon, Alfred A. Bartolucci, Xiaohua Li, Richard S Jope

Research output: Contribution to journalArticle

151 Citations (Scopus)

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 GSK3α/Β 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.

Original languageEnglish
Pages (from-to)1761-1774
Number of pages14
JournalNeuropsychopharmacology
Volume35
Issue number8
DOIs
StatePublished - Jul 1 2010
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Serine
Phosphorylation
Bipolar Disorder
Amphetamine
Alanine
Antidepressive Agents
Antipsychotic Agents
Neurotransmitter Agents
Blood Cells
Mutation
Brain

Keywords

  • Amphetamine
  • Bipolar disorder
  • Depression
  • Glycogen synthase kinase-3
  • Lithium

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. / Polter, Abigail; Beurel, Eleonore; Yang, Sufen; Garner, Rakesha; Song, Ling; Miller, Courtney A.; Sweatt, J. David; McMahon, Lori; Bartolucci, Alfred A.; Li, Xiaohua; Jope, Richard S.

In: Neuropsychopharmacology, Vol. 35, No. 8, 01.07.2010, p. 1761-1774.

Research output: Contribution to journalArticle

Polter, A, Beurel, E, Yang, S, Garner, R, Song, L, Miller, CA, Sweatt, JD, McMahon, L, Bartolucci, AA, Li, X & Jope, RS 2010, 'Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances', Neuropsychopharmacology, vol. 35, no. 8, pp. 1761-1774. https://doi.org/10.1038/npp.2010.43
Polter, Abigail ; Beurel, Eleonore ; Yang, Sufen ; Garner, Rakesha ; Song, Ling ; Miller, Courtney A. ; Sweatt, J. David ; McMahon, Lori ; Bartolucci, Alfred A. ; Li, Xiaohua ; Jope, Richard S. / Deficiency in the inhibitory serine-phosphorylation of glycogen synthase kinase-3 increases sensitivity to mood disturbances. In: Neuropsychopharmacology. 2010 ; Vol. 35, No. 8. pp. 1761-1774.
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