Abstract |
Interest in brain-derived neurotrophic factor ( BDNF) was greatly enhanced when it was recognized that its expression is reduced in neurodegenerative disorders, especially in Alzheimer's disease (AD). BDNF signaling through the TrkB receptor has a central role in promoting synaptic transmission, synaptogenesis, and facilitating synaptic plasticity making the BDNF-TrkB signaling pathway an attractive candidate for targeted therapies. Here we investigated the early effect of the small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), on AD-related pathology, dendritic arborization, synaptic density, and neurochemical changes in the 5xFAD mouse model of AD. We treated 5xFAD mice with 7,8-DHF for 2 months beginning at 1 month of age. We found that, in this model of AD, 7,8-DHF treatment decreased cortical Aβ plaque deposition and protected cortical neurons against reduced dendritic arbor complexity but had no significant impact on the density of dendritic spines. In addition 7,8-DHF treatment protected against hippocampal increase in the level of choline-containing compounds and glutamate loss, but had no significant impact on hippocampal neurogenesis.
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Authors | Nurgul Aytan, Ji-Kyung Choi, Isabel Carreras, Leah Crabtree, Brian Nguyen, Margaret Lehar, Jan Krzysztof Blusztajn, Bruce G Jenkins, Alpaslan Dedeoglu |
Journal | European journal of pharmacology
(Eur J Pharmacol)
Vol. 828
Pg. 9-17
(Jun 05 2018)
ISSN: 1879-0712 [Electronic] Netherlands |
PMID | 29510124
(Publication Type: Journal Article)
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Copyright | Copyright © 2018. Published by Elsevier B.V. |
Chemical References |
- 6,7-dihydroxyflavone
- Amyloid beta-Peptides
- Flavones
- Neuroprotective Agents
- Peptide Fragments
- amyloid beta-protein (1-40)
- amyloid beta-protein (1-42)
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Topics |
- Alzheimer Disease
(metabolism, pathology)
- Amyloid beta-Peptides
(metabolism)
- Animals
- Dendritic Spines
(drug effects, pathology)
- Disease Models, Animal
- Flavones
(pharmacology)
- Hippocampus
(drug effects, metabolism, pathology)
- Mice
- Neuroprotective Agents
(pharmacology)
- Peptide Fragments
(metabolism)
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