Phenotypic Alterations in Hippocampal NPY- and PV-Expressing Interneurons in a Presymptomatic Transgenic Mouse Model of Alzheimer’s Disease
Open accessAbstract
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.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [130]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The mouse brain in stereotaxic coordinates
Konsman, J. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(03)00088-x · Cited by 16,796 · see citing works
The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · see citing works
Alzheimer Mechanisms and Therapeutic Strategies
Huang, Y., & Mucke, L. (2012) · Cell · doi:10.1016/j.cell.2012.02.040 · Cited by 1,758 · see citing works
Palop, J. J., Chin, J., Roberson, E. D., Wang, J., Thwin, M. T., Bien-Ly, N., Yoo, J., Ho, K. O., Yu, G.-Q., Kreitzer, A., et al. (2007) · Neuron · doi:10.1016/j.neuron.2007.07.025 · Cited by 1,653 · see citing works
Amyloid-β–induced neuronal dysfunction in Alzheimer's disease: from synapses toward neural networks
Palop, J. J., & Mucke, L. (2010) · Nature Neuroscience · doi:10.1038/nn.2583 · Cited by 1,651 · see citing works
Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons
Cobb, S. R., Buhl, E. H., Halasy, K., Paulsen, O., & Somogyi, P. (1995) · Nature · doi:10.1038/378075a0 · Cited by 1,498 · see citing works
Verret, L., Mann, E. O., Hang, G. B., Barth, A. M. I., Cobos, I., Ho, K., Devidze, N., Masliah, E., Kreitzer, A. C., Mody, I., et al. (2012) · Cell · doi:10.1016/j.cell.2012.02.046 · Cited by 1,216 · see citing works
Guidotti, A., Auta, J., Davis, J. M., Gerevini, V. D. G., Dwivedi, Y., Grayson, D. R., Impagnatiello, F., Pandey, G. N., Pesold, C., Sharma, R. P., et al. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.11.1061 · Cited by 1,203 · see citing works
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
Hashimoto, T., Volk, D. W., Eggan, S. M., Mirnics, K., Pierri, J. N., Sun, Z., Sampson, A. R., & Lewis, D. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-15-06315.2003 · Cited by 938 · see citing works
A decrease of reelin expression as a putative vulnerability factor in schizophrenia
Impagnatiello, F., Guidotti, A. R., Pesold, C., Dwivedi, Y., Caruncho, H. J., Pisu, M. G., Uzunov, D. P., Smalheiser, N. R., Davis, J. M., Pandey, G. N., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.26.15718 · Cited by 753 · see citing works
An overview of APP processing enzymes and products.
Chow, V. W., Mattson, M. P., Wong, P. C., & Gleichmann, M. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8104-z · Cited by 684 · see citing works
Epilepsy and Cognitive Impairments in Alzheimer Disease
Palop, J. J. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.15 · Cited by 684 · see citing works
Pham, K., Nacher, J., Hof, P. R., & McEwen, B. S. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02513.x · Cited by 657 · see citing works
A Hundred Years of Alzheimer's Disease Research
Hardy, J. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.016 · Cited by 467 · see citing works
Role of GABAergic inhibition in hippocampal network oscillations
Mann, E. O., & Paulsen, O. (2007) · Trends in Neurosciences · doi:10.1016/j.tins.2007.05.003 · Cited by 389 · see citing works
Nalbantoglu, J. N., Santiago, G. T., Lahsaïni, A., Poirier, J., Goncalves, O., Verge, G. M., Momoli, F., Welner, S. A., Massicotte, G., Julien, J., et al. (1997) · Nature · doi:10.1038/387500a0 · Cited by 334 · see citing works
Self-generated theta oscillations in the hippocampus
Goutagny, R., Jackson, J., & Williams, S. (2009) · Nature Neuroscience · doi:10.1038/nn.2440 · Cited by 301 · see citing works
Self-citationGoutagny, R., Gu, N., Cavanagh, C., Jackson, J., Chabot, J., Quirion, R., Krantic, S. M., & Williams, S. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12233 · Cited by 264 · see citing works
Self-citationAvoli, M., & de Curtis, M. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.07.003 · Cited by 255 · see citing works
Parvalbumin interneurons of hippocampus tune population activity at theta frequency
Amilhon, B., Huh, C. Y. L., Manseau, F., Ducharme, G., Nichol, H., Adamantidis, A., & Williams, S. (2015) · Neuron · doi:10.1016/j.neuron.2015.05.027 · Cited by 241 · see citing works
Self-citationLawrence, J. J., & McBain, C. J. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.09.007 · Cited by 214 · see citing works
Ramos, B., Baglietto‐Vargas, D., del Río, J. C., Moreno‐González, I., Santa‐María, C., Jiménez, S., Caballero, C., Lopez-Tellez, J. F., Khan, Z. U., Ruano, D., et al. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.022 · Cited by 213 · see citing works
Maccaferri, G., & Lacaille, J. (2003) · Trends in Neurosciences · doi:10.1016/j.tins.2003.08.002 · Cited by 204 · see citing works
Oster‐Granite, M. L., McPhie, D. L., Greenan, J., & Neve, R. L. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-21-06732.1996 · Cited by 200 · see citing works
Akbarian, S., Smith, M. A., & Jones, E. G. (1995) · Brain Research · doi:10.1016/0006-8993(95)00922-d · Cited by 183 · see citing works
Deregulation of excitatory neurotransmission underlying synapse failure in Alzheimer's disease
Paula‐Lima, A. C., Brito‐Moreira, J., & Ferreira, S. T. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12304 · Cited by 170 · see citing works
Kammesheidt, A., Boyce, F. M., Spanoyannis, A., Cummings, B. J., Ortegón, M. E., Cotman, C. W., Vaught, J. L., & Neve, R. L. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10857 · Cited by 150 · see citing works
Tamayev, R., Matsuda, S., Arancio, O., & D'Adamio, L. (2012) · EMBO Molecular Medicine · doi:10.1002/emmm.201100195 · Cited by 142 · see citing works
Barelli, H., Lebeau, A., Vizzavona, J., Delaère, P., Chevallier, N., Drouot, C., Marambaud, P., Ancolio, K., Buxbaum, J. D., Khorkova, O., et al. (1997) · Molecular Medicine · doi:10.1007/bf03401708 · Cited by 139 · see citing works
Hippocampal interneuron loss in an APP/PS1 double mutant mouse and in Alzheimer’s disease
Takahashi, H., Brasnjevic, I., Rutten, B. P. F., Van Der Kolk, N., Perl, D. P., Bouras, C., Steinbusch, H. W. M., Schmitz, C., Hof, P. R., & Dickstein, D. L. (2010) · Brain Structure and Function · doi:10.1007/s00429-010-0242-4 · Cited by 124 · see citing works
Object recognition memory and BDNF expression are reduced in young TgCRND8 mice
Francis, B. M., Kim, J., Barakat, M., Fraenkl, S. A., Yücel, Y. H., Peng, S., Michalski, B., Fahnestock, M. L., McLaurin, J., & Mount, H. T. J. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.04.003 · Cited by 108 · see citing works
Nava-Mesa, M. O., Jiménez‐Díaz, L., Yajeya, J., & Navarro‐López, J. D. (2014) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2014.00167 · Cited by 105 · see citing works
Palop, J. J., Mucke, L., & Roberson, E. D. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-744-0_17 · Cited by 104 · see citing works
Increased seizure threshold and severity in young transgenic CRND8 mice
Vecchio, R. A. D., Gold, L. H., Novick, S. J., Wong, G., & Hyde, L. A. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.05.107 · Cited by 103 · see citing works
Long-Term Potentiation Is Increased in the CA1 Area of the Hippocampus of APPswe/ind CRND8 Mice
Jolas, T. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2002.0557 · Cited by 98 · see citing works
Lamensdorf, I., Eisenhofer, G., Harvey-White, J. D., Hayakawa, Y., Kirk, K., & Kopin, I. J. (2000) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(20000515)60:4 · Cited by 90 · see citing works
Neve, R. L., Kammesheidt, A., & Höhmann, C. F. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.8.3448 · Cited by 79 · see citing works
Krantic, S., Isorce, N., Mechawar, N., Davoli, M. A., Vignault, E., Albuquerque, M., Chabot, J.-G., Moyse, E., Chauvin, J.-P., Aubert, I., et al. (2012) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110830 · Cited by 78 · see citing works
Self-citationUchida, T., Furukawa, T., Iwata, S., Yanagawa, Y., & Fukuda, A. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.13 · Cited by 73 · see citing works
Albuquerque, M. S., Mahar, I., Davoli, M. A., Chabot, J.-G., Mechawar, N., Quirion, R., & Krantic, S. (2015) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2015.00030 · Cited by 71 · see citing works
Self-citationXu, W., Fitzgerald, S., Nixon, R., Levy, E., & Wilson, D. (2014) · Experimental Neurology · doi:10.1016/j.expneurol.2014.12.008 · Cited by 66 · see citing works
Homeostatic Disinhibition in the Aging Brain and Alzheimer's Disease
Gleichmann, M., Chow, V. W., & Mattson, M. P. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-101674 · Cited by 58 · see citing works
Lagostena, L., Rosato‐Siri, M. D., D’Onofrio, M., Brandi, R., Arisi, I., Capsoni, S., Franzot, J., Cattaneo, A., & Cherubini, E. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3326-09.2010 · Cited by 51 · see citing works
Noori, H., & Fornal, C. (2011) · Frontiers in Neuroscience · doi:10.3389/fnins.2011.00140 · Cited by 50 · see citing works
Entorhinal cortical defects in Tg2576 mice are present as early as 2–4 months of age
Duffy, Á., Morales‐Corraliza, J., Bermudez‐Hernandez, K., Schaner, M. J., Magagna‐Poveda, A., Mathews, P. M., & Scharfman, H. E. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.07.001 · Cited by 49 · see citing works
Region-specific alteration of GABAergic markers in the brain of heterozygous reeler mice
Nullmeier, S., Panther, P., Dobrowolny, H., Frotscher, M., Zhao, S., Schwegler, H., & Wolf, R. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07563.x · Cited by 43 · see citing works
Cavanagh, C., Colby-Milley, J., Bouvier, D. S., Farso, M. C., Chabot, J., Quirion, R., & Krantic, S. M. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-122131 · Cited by 42 · see citing works
Self-citationα7-nAChR agonist enhances neural plasticity in the hippocampus via a GABAergic circuit
Townsend, M., Whyment, A. D., Walczak, J., Jeggo, R., van den Top, M., Flood, D. G., Leventhal, L., Patzke, H., & Koenig, G. (2016) · Journal of Neurophysiology · doi:10.1152/jn.00243.2016 · Cited by 29 · see citing works
Niedringhaus, M. S., Chen, X., & Dzakpasu, R. (2015) · PLoS ONE · doi:10.1371/journal.pone.0129324 · Cited by 5 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Parvalbumin interneuron vulnerability and brain disorders
Ruden, J. B., Dugan, L. L., & Konradi, C. (2021) · Neuropsychopharmacology · doi:10.1038/s41386-020-0778-9 · Cited by 194 · see citing works
Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models
Wirths, O., & Zampar, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21218144 · Cited by 75 · see citing works
Ugolini, F., Lana, D., Nardiello, P., Nosi, D., Pantano, D., Casamenti, F., & Giovannini, M. G. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00372 · Cited by 50 · see citing works
Giesers, N. K., & Wirths, O. (2020) · ASN Neuro · doi:10.1177/1759091420925356 · Cited by 47 · see citing works
- 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
- Publisher
- Frontiers Media SA
- Published
- 2017-01-19
- Volume
- 8
- Pages
- 327-327
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5243860
- 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
- gold
- doi.org
- 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
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 ›
Are you an author, or do you see a problem with this page? Request a review