ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
GSK3β Hyperactivity during an Early Critical Period Impairs Prefrontal Synaptic Plasticity and Induces Lasting Deficits in Spine Morphology and Working Memory.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- Sevoflurane-induced disruption of critical period Arc signaling drives aberrant microglial synaptic pruning and cognitive deficits.Acta pharmacologica Sinica · 2026Article
- Divergent transcriptomic pathways underlie sex-biased cognitive rescue by developmental GSK3B inhibition in a mouse model of 22q11.2 deletion syndrome.Translational psychiatry · 2026Article
- Prefrontal Cortex Dysfunction as a Precipitating Factor for Schizophrenia and Depression.Journal of neurochemistry · 2026Review
- GSK-3β coordinates axonal microtubule organization through Shot and Tau.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.Science advances · 2025Article
- Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.bioRxiv : the preprint server for biology · 2024Article
- Effects of glycogen synthase kinase-3β activity inhibition on cognitive, behavioral, and hippocampal ultrastructural deficits in adulthood associated with adolescent methamphetamine exposure.Frontiers in molecular neuroscience · 2023Article
- α-Glyceryl-phosphoryl-ethanolamine protects human hippocampal neurons from ageing-induced cellular alterations.The European journal of neuroscience · 2022Article
- Distinct Roles for Prefrontal Dopamine D1 and D2 Neurons in Social Hierarchy.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Genotoxic Damage During Brain Development Presages Prototypical Neurodegenerative Disease.Frontiers in neuroscience · 2021Review
- Deletion of Glycogen Synthase Kinase-3β in DBiological psychiatry · 2020Article
- Facilitating Granule Cell Survival and Maturation in Dentate Gyrus With Baicalin for Antidepressant Therapeutics.Frontiers in pharmacology · 2020Article
- LiCl Pretreatment Ameliorates Adolescent Methamphetamine Exposure-Induced Long-Term Alterations in Behavior and Hippocampal Ultrastructure in Adulthood in Mice.The international journal of neuropsychopharmacology · 2019Article
- GSK-3Neural plasticity · 2019Review
- Review
- The histone demethylase KDM6B in the medial prefrontal cortex epigenetically regulates cocaine reward memory.Neuropharmacology · 2018Article
- Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3β.Neuropharmacology · 2018Article
- Altered Behavior in Mice Socially Isolated During Adolescence Corresponds With Immature Dendritic Spine Morphology and Impaired Plasticity in the Prefrontal Cortex.Frontiers in behavioral neuroscience · 2018Article
- Lithium Inhibits GSK3β and Augments GluN2A Receptor Expression in the Prefrontal Cortex.Frontiers in cellular neuroscience · 2018Article
- Epigenetic mechanisms underlying NMDA receptor hypofunction in the prefrontal cortex of juvenile animals in the MAM model for schizophrenia.Journal of neurochemistry · 2017Article
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
Schizophrenia (SZ) is a neurodevelopmental disorder in which the emergence of cognitive symptoms occurs during early adolescence. Glycogen synthase kinase-3β (GSK3β) plays a critical role in synaptic plasticity during development and is highly implicated in the etiology of SZ. However, how GSK3β activity affects synaptic plasticity and working memory function in the prefrontal cortex (PFC) during development remains unknown. Here we show a GSK3β hyperactivity during the early postnatal period in a neurodevelopmental rat SZ model that receives gestational exposure (E17) to the neurotoxin methylazoxymethanol (MAM). Accompanied with this change, adult MAM rats exhibited a significant decrease in spine density as well as impaired working memory, which was rescued by treatment with a GSK3β inhibitor during the juvenile period. Furthermore, the age-dependent hyperactive GSK3β caused a significant deficit in long-term potentiation (LTP) and facilitated long-term depression (LTD) in PFC pyramidal neurons. Notably, these changes in synaptic plasticity occurred only during the late juvenile period and were efficiently reversed by application of GSK3β inhibitors. Because the balance of LTP and LTD plays a critical role in activity-dependent synaptic stabilization and elimination during cortical development, the transient hyperactive GSK3β likely accounts for the cortical spine loss and PFC-dependent cognitive deficits in adulthood. These results highlight the importance of the postnatal trajectory of GSK3β for spine development and PFC function, and may shed light on the prophylactic treatment of cognitive symptoms in the SZ.
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