ArticleMolecular psychiatry2024
Ketamine impairs growth cone and synaptogenesis in human GABAergic projection neurons via GSK-3β and HDAC6 signaling.
Article in Molecular psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Perioperative Adjunctive Esketamine for Postpartum Depression Among Women Undergoing Elective Cesarean Delivery: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Alterations in glutamatergic and GABAergic signaling in ketamine-induced neurotoxicity: mangiferin mitigates neurochemical, oxidative, and astrocytic dysregulation in the rat temporal-frontal cortex.Behavioral and brain functions : BBF · 2026Article
- Ketamine's Role in Neuroinflammation and Neuroprotection Across Neurological and Psychiatric Disorders: A Narrative Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Current Applications of Human Pluripotent Stem Cells in Neuroscience Research and Cell Transplantation Therapy for Neurological Disorders.Stem cell reviews and reports · 2025Review
- Rapid and sustained antidepressant effects of tubastatin A in a mouse model of depression.Scientific reports · 2025Article
- Ketamine does not rescue plaque load or gap detection in the 5XFAD mouse model of Alzheimer's disease.Frontiers in aging neuroscience · 2025Article
- Endogenous mutant Huntingtin alters the corticogenesis via lowering Golgi recruiting ARF1 in cortical organoid.Molecular psychiatry · 2024Article
- Epigenetic mechanisms of rapid-acting antidepressants.Translational psychiatry · 2024Review
- Local delivery of EGFRBioactive materials · 2024Article
- Article
- Machine learning discriminates P2X7-mediated intracellular calcium sparks in human-induced pluripotent stem cell-derived neural stem cells.Scientific reports · 2023Article
- Changes in synaptic markers after administration of ketamine or psychedelics: a systematic scoping review.Frontiers in psychiatry · 2023Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
The growth cone guides the axon or dendrite of striatal GABAergic projection neurons that protrude into the midbrain and cortex and form complex neuronal circuits and synaptic networks in a developing brain, aberrant projections and synaptic connections in the striatum related to multiple brain disorders. Previously, we showed that ketamine, an anesthetic, reduced dendritic growth, dendritic branches, and spine density in human striatal GABAergic neurons. However, whether ketamine affects the growth cone, the synaptic connection of growing striatal GABAergic neurons has not been tested. Using human GABAergic projection neurons derived from human inducible pluripotent stem cells (hiPSCs) and embryonic stem cells (ES) in vitro, we tested ketamine effects on the growth cones and synapses in developing GABAergic neurons by assessing the morphometry and the glycogen synthase kinase-3 (GSK-3) and histone deacetylase 6 (HDAC6) pathway. Ketamine exposure impairs growth cone formation, synaptogenesis, dendritic development, and maturation via ketamine-mediated activation of GSK-3 pathways and inhibiting HDAC6, an essential stabilizing protein for dendritic morphogenesis and synapse maturation. Our findings identified a novel ketamine neurotoxic pathway that depends on GSK-3β and HDAC6 signaling, suggesting that microtubule acetylation is a potential target for reducing ketamine's toxic effect on GABAergic projection neuronal development.
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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 Socratic graph.