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Cited by 107Neurogenesis and neuroplasticity mechanismsAlzheimer's disease research and treatmentsEpilepsy research and treatment

Early Seizure Activity Accelerates Depletion of Hippocampal Neural Stem Cells and Impairs Spatial Discrimination in an Alzheimer’s Disease Model

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Fu, Chia-Hsuan, Iascone, Daniel Maxim, Petrof, Iraklis, Hazra, Anupam, Zhang, Xiaohong, Pyfer, Mark S., Tosi, Umberto, Corbett, Brian F. +7 more·2019·Cell Reports
DOI 10.1016/j.celrep.2019.05.101PMC PMC6697001
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Abstract

Adult hippocampal neurogenesis has been reported to be decreased, increased, or not changed in Alzheimer's disease (AD) patients and related transgenic mouse models. These disparate findings may relate to differences in disease stage, or the presence of seizures, which are associated with AD and can stimulate neurogenesis. In this study, we investigate a transgenic mouse model of AD that exhibits seizures similarly to AD patients and find that neurogenesis is increased in early stages of disease, as spontaneous seizures became evident, but is decreased below control levels as seizures recur. Treatment with the antiseizure drug levetiracetam restores neurogenesis and improves performance in a neurogenesis-associated spatial discrimination task. Our results suggest that seizures stimulate, and later accelerate the depletion of, the hippocampal neural stem cell pool. These results have implications for AD as well as any disorder accompanied by recurrent seizures, such as epilepsy.

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  • In transgenic mice expressing human APP, high levels of Aβ peptide lead to depletion of hippocampal stem cells and impairments in spatial discrimination.

    “leading to depletion of hippocampal stem cells and impairments in spatial discrimination [7, 8]”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [7]

    The Results sections on NSC pool depletion and spatial discrimination (pages not provided) report fewer hippocampal neural stem cells and impaired spatial discrimination in APP mice relative to controls. They do not establish that high Aβ levels caused those outcomes; the Results on levetiracetam instead implicate early seizure activity in stem-cell depletion. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • In transgenic mice expressing human APP, high levels of Aβ peptide are sufficient to induce epileptiform activity and seizures even in the early stages of the disease process.

    “studies using transgenic mice expressing human APP have shown that high levels of Aβ peptide are sufficient to induce epileptiform activity and seizures even in the early stages of the disease process”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [7]

    The Results section reports epileptiform spikes in APP mice by 1 month of age and robust seizures by 2 months, supporting the early-activity part of the claim. It does not establish that high Aβ peptide levels are sufficient to cause either outcome; the study examines mice expressing mutant human APP, not Aβ sufficiency. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Both cell autonomous and non-cell autonomous mechanisms contribute to epilepsy in AD.

    “Recent reports suggest both cell autonomous and non-cell autonomous mechanisms are contributors to epilepsy in AD [7, 10].”

    From Microglia specific deletion of miR-155 in Alzheimer’s disease mouse models reduces amyloid-β pathology but causes hyperexcitability and seizures (2023) · cites this paper as [7]

    The Results section on chronic levetiracetam treatment compares cell-autonomous and circuit-level explanations for altered neural stem cell dynamics, not for epilepsy in AD. The Discussion says that whether altered neurogenesis affects epileptogenesis in these APP mice remains to be assessed. Searches for cell-autonomous and non-cell-autonomous mechanisms of seizures found no passage establishing both as contributors to epilepsy in AD; page numbers were not available in our copy. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Authors
Fu, C.-H., Iascone, D. M., Petrof, I., Hazra, A., Zhang, X., Pyfer, M. S., Tosi, U., Corbett, B. F., Cai, J., Lee, J., Park, J., Iacovitti, L., Scharfman, H. E., Enikolopov, G., & Chin, J.
Affiliations
  • Thomas Jefferson University (US)
  • Baylor College of Medicine (US)
  • NYU Langone Health (US)
  • Stony Brook University (US)
Corresponding author
Chin, Jeannie
ORCID
Venue
Cell Reports
Publisher
Elsevier BV
Published
2019-06
Volume
27
Issue
13
Pages
3741-3751.e4
ISSN
2211-1247 (ISSN-L)
DOI
10.1016/j.celrep.2019.05.101
PMC
PMC6697001
OpenAlex
W2955253088
Cited by
107
References
14
Citations by year
2026: 8 · 2025: 11 · 2024: 28 · 2023: 11 · 2022: 13 · 2021: 25 · 2020: 7 · 2019: 4
FWCI
4.61
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Reports (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health
  • New York State Office of Mental Health
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
Keywords
Alzheimer's disease, seizures, adult hippocampal neurogenesis, neural stem cells, levetiracetam, antiepileptic drugs, spatial discrimination, transgenic mouse model, epilepsy, disease stage
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Hippocampus, Humans, Mice, Transgenic, Seizures, Mice, Neurogenesis, Neural Stem Cells

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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