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Cited by 225Bipolar Disorder and TreatmentTreatment of Major DepressionNeuroscience and Neuropharmacology Research

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

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Polter, Abigail, Beurel, Eléonore, Yang, Sufen, Garner, Rakesha, Song, Ling, Miller, Courtney A, Sweatt, J David, McMahon, Lori +3 more·2010·Neuropsychopharmacology
DOI 10.1038/npp.2010.43PMC PMC2891528
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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.

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  • Exposure to only escapable foot shocks, without a prior session of inescapable foot shocks, causes learned helplessness behavior in a portion of GSK3 knockin mice, but not wild-type mice.

    “Exposure to only escapable foot shocks, without a prior session of inescapable foot shocks, causes learned helplessness behavior in a portion of GSK3 knockin mice, but not wild-type mice (34).”

    From Inflammatory T helper 17 cells promote depression-like behavior in mice (2013) · cites this paper as [34]

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Authors
Polter, A., Beurel, E., Yang, S., Garner, R., Song, L., Miller, C. A., Sweatt, J. D., McMahon, L., Bartolucci, A. A., Li, X., & Jope, R. S.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
  • Li, Xiaohua
  • Jope, Richard S
ORCID
Venue
Neuropsychopharmacology
Publisher
Springer Science and Business Media LLC
Published
2010-03-31
Volume
35
Issue
8
Pages
1761-1774
ISSN
  • 0893-133X (ISSN-L)
  • 1740-634X
DOI
10.1038/npp.2010.43
PMC
PMC2891528
OpenAlex
W1988375440
Cited by
225
References
6
Citations by year
2026: 1 · 2025: 3 · 2024: 5 · 2023: 10 · 2022: 12 · 2021: 12 · 2020: 11 · 2019: 9 · 2018: 10 · 2017: 16 · 2016: 19 · 2015: 20 · 2014: 24 · 2013: 20 · 2012: 21
FWCI
15.96
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Neuropsychopharmacology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Brain Research Foundation
  • McKnight Foundation
  • Evelyn F. McKnight Brain Research Foundation
  • National Alliance for Research on Schizophrenia and Depression
  • National Institutes of Health (MH38752, NS47466, MH64555, MH73723)
  • National Institute on Aging (R01AG021612)
  • National Institute of Mental Health (R01MH073723, MH38752, MH64555, K02MH086622, MH 57014, R56MH038752, K08MH064555, MH73723, MH82304, R01MH038752, R01MH057014, MH86622, R01MH082304)
  • National Institute of Neurological Disorders and Stroke (NS47466, P30NS047466, NS61788, T32NS061788)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
glycogen synthase kinase-3, serine phosphorylation, bipolar disorder, mood stabilization, amphetamine-induced hyperactivity, stress-induced depression, depression-like behavior, mood stabilizers, blood cells
MeSH terms
Adult, Aged, Animals, Behavior, Animal, Conditioning, Psychological, Disease Models, Animal, Electroshock, Enzyme-Linked Immunosorbent Assay, Exploratory Behavior, Fear, Female, Helplessness, Learned, Hippocampus, Humans, Male, Middle Aged, Pain, Phosphorylation, Serine, Swimming, Pain Threshold, Long-Term Potentiation, Mice, Knockout, Maze Learning, Mood Disorders, Glycogen Synthase Kinase 3, Mice, In Vitro Techniques

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