Cited by 63Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchDementia and Cognitive Impairment Research

Phenotypic Alterations in Hippocampal NPY- and PV-Expressing Interneurons in a Presymptomatic Transgenic Mouse Model of Alzheimer’s Disease

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Mahar, Ian, Albuquerque, Marilia Silva, Mondragon-Rodriguez, Siddhartha, Cavanagh, Chelsea, Davoli, Maria Antonietta, Chabot, Jean-Guy, Williams, Sylvain, Mechawar, Naguib +2 more·2017·Frontiers in Aging Neuroscience

Abstract

Interneurons, key regulators of hippocampal neuronal network excitability and synchronization, are lost in advanced stages of Alzheimer's disease (AD). Given that network changes occur at early (presymptomatic) stages, we explored whether alterations of interneurons also occur before amyloid-beta (Aβ) accumulation. Numbers of neuropeptide Y (NPY) and parvalbumin (PV) immunoreactive (IR) cells were decreased in the hippocampus of 1 month-old TgCRND8 mouse AD model in a sub-regionally specific manner. The most prominent change observed was a decrease in the number of PV-IR cells that selectively affected CA1/2 and subiculum, with the pyramidal layer (PY) of CA1/2 accounting almost entirely for the reduction in number of hippocampal PV-IR cells. As PV neurons were decreased selectively in CA1/2 and subiculum, and given that they are critically involved in the control of hippocampal theta oscillations, we then assessed intrinsic theta oscillations in these regions after a 4-aminopyridine (4AP) challenge. This revealed increased theta power and population bursts in TgCRND8 mice compared to non-transgenic (nTg) controls, suggesting a hyperexcitability network state. Taken together, our results identify for the first time AD-related alterations in hippocampal interneuron function as early as at 1 month of age. These early functional alterations occurring before amyloid deposition may contribute to cognitive dysfunction in AD.

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Crossref · 10.3389/fnagi.2016.00327

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  • In TgCRND8 mice, significantly reduced numbers of PV-positive interneurons in the CA1/2 layer were detected at 1 month of age, preceding extracellular plaque deposition.

    “In TgCRND8 mice, a model expressing human mutant APP with the Swedish and Indiana mutations and an early onset of plaque deposition at 3 months of age [39], significantly reduced numbers of PV-positive interneurons in the CA1/2 layer were detected at only 1 month of age, a time point preceding extracellular plaque deposition [130].”

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Authors
Mahar, I., Albuquerque, M. S., Mondragon-Rodriguez, S., Cavanagh, C., Davoli, M. A., Chabot, J.-G., Williams, S., Mechawar, N., Quirion, R., & Krantic, S.
Affiliations
  • Douglas Mental Health University Institute (CA)
  • Universidade de São Paulo (BR)
  • Inserm (FR)
Corresponding author
Krantic, Slavica
Venue
Frontiers in Aging Neuroscience
Published
2017-01-19
Volume
8
Pages
327-327
ISSN
1663-4365 (ISSN-L)
OpenAlex
W2576715432
Cited by
63
References
52
Citations by year
2026: 1 · 2025: 7 · 2024: 6 · 2023: 9 · 2022: 10 · 2021: 6 · 2020: 10 · 2019: 3 · 2018: 10 · 2017: 1
FWCI
4.86
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Aging Neuroscience (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, cc-by)
  • HAL (submittedVersion)
  • Greater South Information System
Funders
Fondation pour la Recherche Médicale (DVS20131228910)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, hippocampal interneurons, parvalbumin interneurons, preclinical Alzheimer's disease, subiculum, theta oscillations, 4-aminopyridine, amyloid-beta, cognitive impairment

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