ArticlePLoS genetics2015
Postnatal loss of hap1 reduces hippocampal neurogenesis and causes adult depressive-like behavior in mice.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Golgi-Cox Staining Protocol for Medium Spiny Neurons in the Striatum of Neonatal and Early Postnatal Mouse Brain Using Cryosections.International journal of molecular sciences · 2025Article
- Mechanistic insights into sevoflurane-induced hippocampal neuronal damage and cognitive dysfunction through the NEAT1/Nrf2 signaling axis in aged rats.Cell biology and toxicology · 2024Article
- Research advances in huntingtin-associated protein 1 and its application prospects in diseases.Frontiers in neuroscience · 2024Review
- Differential expression and roles of Huntingtin and Huntingtin-associated protein 1 in the mouse and primate brains.Cellular and molecular life sciences : CMLS · 2022Article
- Integrated Multi-Omics Analysis Reveals the Effect of Maternal Gestational Diabetes on Fetal Mouse Hippocampi.Frontiers in cell and developmental biology · 2022Article
- Dexamethasone Protects Against Ischaemic Brain Injury via Inhibiting the pAkt Signalling Pathway Through Increasing Hap1.Neurotoxicity research · 2021Article
- Huntingtin-associated protein 1 plays an essential role in the pathogenesis of type 2 diabetes by regulating the translocation of GLUT4 in mouse adipocytes.BMJ open diabetes research & care · 2020Article
- Expression of AHI1 Rescues Amyloidogenic Pathology in Alzheimer's Disease Model Cells.Molecular neurobiology · 2019Article
- Open chromatin dynamics reveals stage-specific transcriptional networks in hiPSC-based neurodevelopmental model.Stem cell research · 2018Article
- Mast cells increase adult neural precursor proliferation and differentiation but this potential is not realized in vivo under physiological conditions.Scientific reports · 2017Article
- A pilot investigation on DNA methylation modifications associated with complex posttraumatic symptoms in elderly traumatized in childhood.BMC research notes · 2017Article
- Synergistic Toxicity of Polyglutamine-Expanded TATA-Binding Protein in Glia and Neuronal Cells: Therapeutic Implications for Spinocerebellar Ataxia 17.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- DYRK1A regulates Hap1-Dcaf7/WDR68 binding with implication for delayed growth in Down syndrome.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Whole exome sequencing of Rett syndrome-like patients reveals the mutational diversity of the clinical phenotype.Human genetics · 2016Article
- Huntingtin-associated protein 1: Eutherian adaptation from a TRAK-like protein, conserved gene promoter elements, and localization in the human intestine.BMC evolutionary biology · 2016Article
- Article
- Exosomes as Novel Regulators of Adult Neurogenic Niches.Frontiers in cellular neuroscience · 2015Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Depression is a serious mental disorder that affects a person's mood, thoughts, behavior, physical health, and life in general. Despite our continuous efforts to understand the disease, the etiology of depressive behavior remains perplexing. Recently, aberrant early life or postnatal neurogenesis has been linked to adult depressive behavior; however, genetic evidence for this is still lacking. Here we genetically depleted the expression of huntingtin-associated protein 1 (Hap1) in mice at various ages or in selective brain regions. Depletion of Hap1 in the early postnatal period, but not later life, led to a depressive-like phenotype when the mice reached adulthood. Deletion of Hap1 in adult mice rendered the mice more susceptible to stress-induced depressive-like behavior. Furthermore, early Hap1 depletion impaired postnatal neurogenesis in the dentate gyrus (DG) of the hippocampus and reduced the level of c-kit, a protein expressed in neuroproliferative zones of the rodent brain and that is stabilized by Hap1. Importantly, stereotaxically injected adeno-associated virus (AAV) that directs the expression of c-kit in the hippocampus promoted postnatal hippocampal neurogenesis and ameliorated the depressive-like phenotype in conditional Hap1 KO mice, indicating a link between postnatal-born hippocampal neurons and adult depression. Our results demonstrate critical roles for Hap1 and c-kit in postnatal neurogenesis and adult depressive behavior, and also suggest that genetic variations affecting postnatal neurogenesis may lead to adult depression.
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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.