ArticleGenes, brain, and behavior2016
GSK3β isoform-selective regulation of depression, memory and hippocampal cell proliferation.
Article in Genes, brain, and behavior, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Neuroimaging genomic studies in major depressive disorder: A systematic review.CNS neuroscience & therapeutics · 2018Pooled it
- The Differential Involvement of α1-Adrenoceptor Subtypes in the Molecular Effects of Antidepressant Drugs.International journal of molecular sciences · 2025Article
- Role of Phosphorylation of Serotonin and Norepinephrine Transporters in Animal Behavior: Relevance to Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Neuroprotective potential of hispidulin and diosmin: a review of molecular mechanisms.Metabolic brain disease · 2025Review
- Understanding Glycogen Synthase Kinase-3: A Novel Avenue for Alzheimer's Disease.Molecular neurobiology · 2024Review
- Targeting the postsynaptic scaffolding protein PSD-95 enhances BDNF signaling to mitigate depression-like behaviors in mice.Science signaling · 2024Article
- Dimethyl itaconate ameliorates the deficits of goal-directed behavior in Toxoplasma gondii infected mice.PLoS neglected tropical diseases · 2023Article
- Dopamine depletion alters neuroplasticity-related signaling in the rat hippocampus.Animal cells and systems · 2023Article
- GSK3β rs3107669 polymorphism implicates chemotherapy-associated retrospective memory deficits in breast cancer survivors.American journal of cancer research · 2023Article
- The role of glycogen synthase kinase 3 beta in neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- Comparison of inflammatory and behavioral responses to chronic stress in female and male mice.Brain, behavior, and immunity · 2022Article
- A possible mechanism to the antidepressant-like effects of 20 (S)-protopanaxadiol based on its target protein 14-3-3 ζ.Journal of ginseng research · 2022Article
- Nk3R blockade has sex-divergent effects on memory in mice.Biology of sex differences · 2022Article
- Resveratrol Protects SH-SY5Y Cells Against Oleic Acid-Induced Glucolipid Metabolic Dysfunction and Cell Injuries Via the Wnt/β-Catenin Signalling Pathway.Neurochemical research · 2021Article
- Opposing Roles of GSK3α and GSK3β Phosphorylation in Platelet Function and Thrombosis.International journal of molecular sciences · 2021Article
- Deficits in pattern separation and dentate gyrus proliferation after rodent lateral fluid percussion injury.IBRO neuroscience reports · 2021Article
- Article
- Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine.International journal of molecular sciences · 2021Review
- Glycogen synthase kinase-3ß supports serotonin transporter function and trafficking in a phosphorylation-dependent manner.Journal of neurochemistry · 2021Article
- Network Pharmacology and Experimental Evidence: PI3K/AKT Signaling Pathway is Involved in the Antidepressive Roles of Chaihu Shugan San.Drug design, development and therapy · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Abnormally active glycogen synthase kinase-3 (GSK3) contributes to pathological processes in multiple psychiatric and neurological disorders. Modeled in mice, this includes increasing susceptibility to dysregulation of mood-relevant behaviors, impairing performance in several cognitive tasks and impairing adult hippocampal neural precursor cell (NPC) proliferation. These deficits are all evident in GSK3α/β knockin mice, in which serine-to-alanine mutations block the inhibitory serine phosphorylation regulation of both GSK3 isoforms, leaving GSK3 hyperactive. It was unknown if both GSK3 isoforms perform redundant actions in these processes, or if hyperactivity of one GSK3 isoform has a predominant effect. To test this, we examined GSK3α or GSK3β knockin mice in which only one isoform was mutated to a hyperactive form. Only GSK3β, not GSK3α, knockin mice displayed heightened vulnerability to the learned helplessness model of depression-like behavior. Three cognitive measures impaired in GSK3α/β knockin mice showed differential regulation by GSK3 isoforms. Novel object recognition was impaired in GSK3β, not in GSK3α, knockin mice, whereas temporal order memory was not impaired in GSK3α or GSK3β knockin mice, and co-ordinate spatial processing was impaired in both GSK3α and GSK3β knockin mice. Adult hippocampal NPC proliferation was severely impaired in GSK3β knockin mice, but not impaired in GSK3α knockin mice. Increased activity of GSK3β, in the absence of overexpression or disease pathology, is sufficient to impair mood regulation, novel object recognition and hippocampal NPC proliferation, whereas hyperactive GSK3α individually does not impair these processes. These results show that hyperactivity of the two GSK3 isoforms execute non-redundant effects on these processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.