ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Functional and mechanistic exploration of an adult neurogenesis-promoting small molecule.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
39 citing papers in PubMed, 71 citations in OpenAlex.
- Article
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- In Vitro and In Vivo Direct Reprogramming of Astrocytes to Induced-Neurons.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Obesity and Depression: Common Link and Possible Targets.CNS & neurological disorders drug targets · 2024Review
- An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis.EMBO reports · 2024Article
- Tumor-suppressive disruption of cancer subtype-associated super enhancer circuits by small molecule treatment.NAR cancer · 2023Article
- MRTF specifies a muscle-like contractile module in Porifera.Nature communications · 2022Article
- Pharmacological Perturbation of Mechanical Contractility Enables Robust Transdifferentiation of Human Fibroblasts into Neurons.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Isoxazole-9 reduces enhanced fear responses and retrieval in ethanol-dependent male rats.Journal of neuroscience research · 2021Article
- Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy.Cancers · 2021Article
- Direct Neuronal Reprogramming: Bridging the Gap Between Basic Science and Clinical Application.Frontiers in cell and developmental biology · 2021Review
- Reduced GluN1 in mouse dentate gyrus is associated with CA3 hyperactivity and psychosis-like behaviors.Molecular psychiatry · 2020Article
- Alleviation of Depression by Glucagon-Like Peptide 1 Through the Regulation of Neuroinflammation, Neurotransmitters, Neurogenesis, and Synaptic Function.Frontiers in pharmacology · 2020Review
- Exposure to small molecule cocktails allows induction of neural crest lineage cells from human adipose-derived mesenchymal stem cells.PloS one · 2020Article
- Modes of division and differentiation of neural stem cells.Behavioural brain research · 2019Review
- Rapid and Efficient Conversion of Human Fibroblasts into Functional Neurons by Small Molecules.Stem cell reports · 2019Article
- The role of hippocampal adult neurogenesis in methamphetamine addiction.Brain plasticity (Amsterdam, Netherlands) · 2018Review
- A synthetic small-molecule Isoxazole-9 protects against methamphetamine relapse.Molecular psychiatry · 2018Article
- Dentate gyrus neurogenesis ablation via cranial irradiation enhances morphine self-administration and locomotor sensitization.Addiction biology · 2018Article
- Generation of Functional Dopaminergic Neurons from Reprogramming Fibroblasts by Nonviral-based Mesoporous Silica Nanoparticles.Scientific reports · 2018Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Adult neurogenesis occurs throughout life in the mammalian hippocampus and is essential for memory and mood control. There is significant interest in identifying ways to promote neurogenesis and ensure maintenance of these hippocampal functions. Previous work with a synthetic small molecule, isoxazole 9 (Isx-9), highlighted its neuronal-differentiating properties in vitro. However, the ability of Isx-9 to drive neurogenesis in vivo or improve hippocampal function was unknown. Here we show that Isx-9 promotes neurogenesis in vivo, enhancing the proliferation and differentiation of hippocampal subgranular zone (SGZ) neuroblasts, and the dendritic arborization of adult-generated dentate gyrus neurons. Isx-9 also improves hippocampal function, enhancing memory in the Morris water maze. Notably, Isx-9 enhances neurogenesis and memory without detectable increases in cellular or animal activity or vascularization. Molecular exploration of Isx-9-induced regulation of neurogenesis (via FACS and microarray of SGZ stem and progenitor cells) suggested the involvement of the myocyte-enhancer family of proteins (Mef2). Indeed, transgenic-mediated inducible knockout of all brain-enriched Mef2 isoforms (Mef2a/c/d) specifically from neural stem cells and their progeny confirmed Mef2's requirement for Isx-9-induced increase in hippocampal neurogenesis. Thus, Isx-9 enhances hippocampal neurogenesis and memory in vivo, and its effects are reliant on Mef2, revealing a novel cell-intrinsic molecular pathway regulating adult neurogenesis.
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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.