7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer’s Disease
Open accessAbstract
Synaptic loss in the brain correlates well with disease severity in Alzheimer disease (AD). Deficits in brain-derived neurotrophic factor/tropomyosin-receptor-kinase B (TrkB) signaling contribute to the synaptic dysfunction of AD. We have recently identified 7,8-dihydroxyflavone (7,8-DHF) as a potent TrkB agonist that displays therapeutic efficacy toward various neurological diseases. Here we tested the effect of 7,8-DHF on synaptic function in an AD model both in vitro and in vivo. 7,8-DHF protected primary neurons from Aβ-induced toxicity and promoted dendrite branching and synaptogenesis. Chronic oral administration of 7,8-DHF activated TrkB signaling and prevented Aβ deposition in transgenic mice that coexpress five familial Alzheimer's disease mutations (5XFAD mice). Moreover, 7,8-DHF inhibited the loss of hippocampal synapses, restored synapse number and synaptic plasticity, and prevented memory deficits. These results suggest that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating 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?
DHF restores memory deficits in 5XFAD and APP/PS1 mouse models of Alzheimer's disease after acute and chronic administration.
“Indeed, restoration of memory deficits in 5XFAD and APP/PS1 mouse models of Alzheimer’s disease (AD) have been shown after both acute and chronic administration of DHF (Bollen et al. 2013; Devi and Ohno 2012; Zhang et al. 2014c)”
From Neurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression (2018) · cites this paper as Zhang et al. 2014c
The section “Chronic Oral Administration of 7,8-DHF Rescues Memory Deficits in 5XFAD Mice” reports rescued spatial memory after chronic treatment. The Introduction also describes a prior 10-day 5XFAD study, but this paper does not establish memory restoration after acute administration or in APP/PS1 mice. Page numbers were not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured
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
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530 · cited 1× · see citing works
“5XFAD mice have been shown to develop cerebral amyloid plaques at 2 months of age and show memory impairment at 4–5 months of age (Oakley et al, 2006).”
BackgroundNLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice
Heneka, M. T., Kummer, M. P., Stutz, A., Delekate, A., Schwartz, S., Vieira-Saecker, A., Griep, A., Axt, D., Remus, A., Tzeng, T.-C., et al. (2013) · Nature · doi:10.1038/nature11729 · Cited by 2,898 · see citing works
SZE, C.-I., TRONCOSO, J. C., KAWAS, C., MOUTION, P., PRICE, D. L., & MARTIN, L. J. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199708000-00011 · Cited by 562 · cited 2× · see citing works
“Furthermore, synaptic loss appears to be the best pathologic correlate of dementia in AD (Sze et al, 1997; Terry et al, 1991).”
BackgroundOchs, G., Penn, R. D., York, M., Giess, R., Beck, M., Tonn, J., Haigh, J., Malta, E., Traub, M., Sendtner, M., et al. (2000) · Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders · doi:10.1080/14660820050515197 · Cited by 302 · see citing works
Regional specificity of alterations in NGF, BDNF and NT-3 levels in Alzheimerʼs disease
Narisawa-Saito, M., Wakabayashi, K., Tsuji, S., Takahashi, H., & Nawa, H. (1996) · NeuroReport · doi:10.1097/00001756-199611250-00024 · Cited by 226 · cited 1× · see citing works
“It has been documented that BDNF expression is reduced in the hippocampus, dentate gyrus, neocortex, and in the nucleus basalis of Meynert of AD patients (Murer et al, 2001; Narisawa-Saito et al, 1996; Phillips et al, 1991).”
BackgroundPrelimbic cortical BDNF is required for memory of learned fear but not extinction or innate fear
Choi, D. C., Maguschak, K. A., Ye, K., Jang, S.-W., Myers, K. M., & Ressler, K. J. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909359107 · Cited by 212 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
FSH blockade improves cognition in mice with Alzheimer’s disease
Xiong, J., Kang, S. S., Wang, Z., Liu, X., Kuo, T.-C., Korkmaz, F., Padilla, A., Miyashita, S., Chan, P., Zhang, Z., et al. (2022) · Nature · doi:10.1038/s41586-022-04463-0 · Cited by 329 · see citing works
Self-citationNeurotrophic factors and neuroplasticity pathways in the pathophysiology and treatment of depression
Levy, M. J. F., Boulle, F., Steinbusch, H. W., van den Hove, D. L. A., Kenis, G., & Lanfumey, L. (2018) · Psychopharmacology · doi:10.1007/s00213-018-4950-4 · Cited by 308 · see citing works
Chen, C., Ahn, E. H., Kang, S. S., Liu, X., Alam, A., & Ye, K. (2020) · Science Advances · doi:10.1126/sciadv.aba0466 · Cited by 205 · see citing works
Self-citationLiu, C., Chan, C. B., & Ye, K. (2016) · Translational Neurodegeneration · doi:10.1186/s40035-015-0048-7 · Cited by 195 · see citing works
Self-citationInhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer’s disease
Zhang, Z., Obianyo, O., Dall, E., Du, Y., Fu, H., Liu, X., Kang, S. S., Song, M., Yu, S.-P., Cabrele, C., et al. (2017) · Nature Communications · doi:10.1038/ncomms14740 · Cited by 146 · see citing works
Self-citationRichard, B. C., Kurdakova, A., Baches, S., Bayer, T. A., Weggen, S., & Wirths, O. (2015) · Journal of Alzheimer’s Disease · doi:10.3233/jad-143120 · Cited by 142 · see citing works
Tejeda, G., & Díaz-Guerra, M. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18020268 · Cited by 126 · see citing works
Neurotrophin receptor agonists and antagonists as therapeutic agents: An evolving paradigm
Josephy-Hernandez, S., Jmaeff, S., Pirvulescu, I., Aboulkassim, T., & Saragovi, H. U. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.08.004 · Cited by 54 · see citing works
Wu, Z., Xia, Y., Wang, Z., Su Kang, S., Lei, K., Liu, X., Jin, L., Wang, X., Cheng, L., & Ye, K. (2021) · Molecular Psychiatry · doi:10.1038/s41380-020-0687-7 · Cited by 41 · see citing works
Self-citationWong, A. W., Giuffrida, L., Wood, R., Peckham, H., Gonsalvez, D., Murray, S. S., Hughes, R. A., & Xiao, J. (2014) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2014.10.002 · Cited by 39 · see citing works
Herzer, S., Hagan, C., von Gerichten, J., Dieterle, V., Munteanu, B., Sandhoff, R., Hopf, C., & Nordström, V. (2018) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2018.00206 · Cited by 27 · see citing works
- Authors
- Zhang, Z., Liu, X., Schroeder, J. P., Chan, C.-B., Song, M., Yu, S. P., Weinshenker, D., & Ye, K.
- Affiliations
- Emory University (US)
- Corresponding author
- Ye, Keqiang
- Venue
- Neuropsychopharmacology
- Published
- 2013-09-11
- Volume
- 39
- Issue
- 3
- Pages
- 638-650
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC3895241
- OpenAlex
- W2004855983
- Cited by
- 242
- References
- 7
- Citations by year
- 2026: 14 · 2025: 9 · 2024: 24 · 2023: 28 · 2022: 21 · 2021: 25 · 2020: 22 · 2019: 13 · 2018: 18 · 2017: 20 · 2016: 23 · 2015: 16 · 2014: 9
- FWCI
- 11.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81100958)
- National Institutes of Health
- National Institute on Aging (P50AG025688)
- National Institute on Deafness and Other Communication Disorders (R01DC010204)
- National Institute of Neurological Disorders and Stroke (R01NS045627)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- 7,8-dihydroxyflavone, Alzheimer's disease, synaptic loss, TrkB signaling, brain-derived neurotrophic factor, amyloid-beta, 5xFAD mice, hippocampal synapses, synaptogenesis, dendritic branching, memory impairment, synaptic plasticity, neuroprotection
- MeSH terms
- Alzheimer Disease, Animals, Cells, Cultured, Cerebral Cortex, Disease Models, Animal, Female, Hippocampus, Humans, Memory Disorders, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neurons, Synapses, Antipsychotic Agents, Amyloid beta-Protein Precursor, Apoptosis, Maze Learning, Flavones, Mice, Plaque, Amyloid, In Vitro Techniques
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
