Cited by 123Neurogenesis and neuroplasticity mechanismsAlzheimer's disease research and treatmentsMemory and Neural Mechanisms

Inhibitory Interneuron Progenitor Transplantation Restores Normal Learning and Memory in ApoE4 Knock-In Mice without or with Aβ Accumulation

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Tong, Leslie M., Djukic, Biljana, Arnold, Christine, Gillespie, Anna K., Yoon, Seo Yeon, Wang, Max M., Zhang, Olivia, Knoferle, Johanna +3 more·2014·The Journal of Neuroscience

Abstract

Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function and may be of particular importance to memory. Apolipoprotein (apo) E4 and amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause inhibitory interneuron impairments and aberrant neuronal activity in the hippocampal dentate gyrus in AD-related mouse models and humans, leading to learning and memory deficits. To determine whether replacing the lost or impaired interneurons rescues neuronal signaling and behavioral deficits, we transplanted embryonic interneuron progenitors into the hippocampal hilus of aged apoE4 knock-in mice without or with Aβ accumulation. In both conditions, the transplanted cells developed into mature interneurons, functionally integrated into the hippocampal circuitry, and restored normal learning and memory. Thus, restricted hilar transplantation of inhibitory interneurons restores normal cognitive function in two widely used AD-related mouse models, highlighting the importance of interneuron impairments in AD pathogenesis and the potential of cell replacement therapy for AD. More broadly, it demonstrates that excitatory and inhibitory balance are crucial for learning and memory, and suggests an avenue for investigating the processes of learning and memory and their alterations in healthy aging and diseases.

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Crossref · 10.1523/jneurosci.0693-14.2014

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  • Transplantation of mouse MGE-derived GABAergic progenitors into aged apoE4-KI mice without or with Aβ accumulation rescues learning and memory deficits.

    “transplantation of mouse MGE-derived GABAergic progenitors into aged apoE4-KI mice without or with Aβ accumulation rescues learning and memory deficits [127].”

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Authors
Tong, L. M., Djukic, B., Arnold, C., Gillespie, A. K., Yoon, S. Y., Wang, M. M., Zhang, O., Knoferle, J., Rubenstein, J. L. R., Alvarez-Buylla, A., & Huang, Y.
Affiliations
  • Gladstone Institutes (US)
  • Neurological Surgery (US)
Venue
The Journal of Neuroscience
Published
2014-07-16
Volume
34
Issue
29
Pages
9506-9515
ISSN
  • 0270-6474 (ISSN-L)
  • 1529-2401
OpenAlex
W2135782855
Cited by
123
References
42
Citations by year
2026: 5 · 2025: 11 · 2024: 6 · 2023: 9 · 2022: 9 · 2021: 13 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 13 · 2016: 17 · 2015: 14 · 2014: 2
FWCI
5.33
Type
journal article
Language
en
Open access
Locations
  • Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by-nc-sa)
Funders
  • S. D. Bechtel, Jr. Foundation and Stephen Bechtel Fund
  • Roddenberry Foundation
  • Hellman Foundation
  • National Institutes of Health (AG‐022074)
  • National Institute on Aging (AG022074, P01AG022074)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD007470)
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
Keywords
amyloid-beta deposition, Alzheimer's disease, dentate gyrus, hippocampal hilus, excitation-inhibition balance, learning and memory impairment, cell replacement therapy, aged mice
MeSH terms
Alzheimer Disease, Animals, Disease Models, Animal, Female, Hippocampus, Humans, Interneurons, Learning, Male, Memory, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Nerve Tissue Proteins, Amyloid beta-Protein Precursor, Maze Learning, Mice, Apolipoprotein E4, Neural Stem Cells, In Vitro Techniques

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