ArticleMolecular neurodegeneration2017
Depletion of adult neurogenesis exacerbates cognitive deficits in Alzheimer's disease by compromising hippocampal inhibition.
Article in Molecular neurodegeneration, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97 citing papers in PubMed, 144 citations in OpenAlex.
- Bisphenol-A impairs hippocampal neurogenesis by disrupting kinesin-1-dependent mitochondrial trafficking.The Journal of biological chemistry · 2026Article
- BDNF-Hyaluronic Acid Hydrogel Promotes Neuronal Differentiation of Neural Stem Cells in Aβ-Induced Injury and 5×FAD Mice.Biomedicines · 2026Article
- Microglia regulate adult neurogenesis via interleukin-6Research square · 2026Article
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- p75 neurotrophin receptor shapes the dynamics of adult hippocampal neurogenesis in Alzheimer's disease.Alzheimer's research & therapy · 2026Article
- Polyphenol diet and exercise as neuroprotective factors in a Drosophila model of Alzheimer's disease.Animal models and experimental medicine · 2026Article
- The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases.Biology · 2025Review
- Boosting Neurogenesis as a Strategy in Treating Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Adult hippocampal neurogenesis: New avenues for treatment of brain disorders.Stem cell reports · 2025Review
- Combating cognitive decline in a rat model of Alzheimer's disease: The role of high-intensity interval training and cannabidiol administration in modulating microRNA-124, BACE1, and nestin.Current journal of neurology · 2025Article
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Review
- Sex-specific influences of APOEε4 genotype on hippocampal neurogenesis and progenitor cells in middle-aged rats.Biology of sex differences · 2025Article
- The active metabolite of Epimedii Folium promotes hippocampal neurogenesis in APP/PS1 mice by alleviating mitochondrial dysfunction.Frontiers in pharmacology · 2025Article
- Decoding senescence of aging single cells at the nexus of biomaterials, microfluidics, and spatial omics.npj aging · 2024Review
- New BDNF and NT-3 Cyclic Mimetics Concur with Copper to Activate Trophic Signaling Pathways as Potential Molecular Entities to Protect Old Brains from Neurodegeneration.Biomolecules · 2024Article
- Leptin receptor reactivation restores brain function in early-life Lepr-deficient mice.Brain : a journal of neurology · 2024Article
- Sex as a Determinant of Age-Related Changes in the Brain.International journal of molecular sciences · 2024Review
- ATG5 (autophagy related 5) in microglia controls hippocampal neurogenesis in Alzheimer disease.Autophagy · 2024Article
- Early Growth Response Gene-1 Deficiency Interrupts TGFβ1 Signaling Activation and Aggravates Neurodegeneration in Experimental Autoimmune Encephalomyelitis Mice.Neuroscience bulletin · 2024Article
37 more citing papers are in PubMed but not listed here.
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8 authors at 2 institutions in 1 country.
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Abstract
backgroundThe molecular mechanism underlying progressive memory loss in Alzheimer's disease is poorly understood. Neurogenesis in the adult hippocampus is a dynamic process that continuously changes the dentate gyrus and is important for hippocampal plasticity, learning and memory. However, whether impairments in neurogenesis affect the hippocampal circuitry in a way that leads to memory deficits characteristic of Alzheimer's disease is unknown. Controversial results in that regard were reported in transgenic mouse models of amyloidosis.
methodsHere, we conditionally ablated adult neurogenesis in APPswe/PS1ΔE9 mice by crossing these with mice expressing nestin-driven thymidine kinase (δ-HSV-TK).
resultsThese animals show impairment in performance in contextual conditioning and pattern separation tasks following depletion of neurogenesis. Importantly, these deficits were not observed in age-matched APPswe/PS1ΔE9 or δ-HSV-TK mice alone. Furthermore, we show that cognitive deficits were accompanied by the upregulation of hyperphosphorylated tau in the hippocampus and in immature neurons specifically. Interestingly, we observed upregulation of the immediate early gene Zif268 (Egr-1) in the dentate gyrus, CA1 and CA3 regions of the hippocampus following learning in the neurogenesis-depleted δ-HSV-TK mice. This may suggest overactivation of hippocampal neurons in these areas following depletion of neurogenesis.
conclusionsThese results imply that neurogenesis plays an important role in the regulation of inhibitory circuitry of the hippocampus. This study suggests that deficits in adult neurogenesis may contribute to cognitive impairments, tau hyperphosphorylation in new neurons and compromised hippocampal circuitry in Alzheimer's disease.
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