7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer's Disease
In: Neuropsychopharmacology (New York, NY), Jg. 39 (2014), Heft 3, S. 638-650
Online
academicJournal
- print; 13; 1 p.1/4
Zugriff:
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.
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7,8-Dihydroxyflavone Prevents Synaptic Loss and Memory Deficits in a Mouse Model of Alzheimer's Disease
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Autor/in / Beteiligte Person: | ZHENTAO, ZHANG ; XIA, LIU ; SCHROEDER, Jason P ; CHAN, Chi-Bun ; MINGKE, SONG ; SHAN PING, YU ; WEINSHENKER, David ; KEQIANG, YE |
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Zeitschrift: | Neuropsychopharmacology (New York, NY), Jg. 39 (2014), Heft 3, S. 638-650 |
Veröffentlichung: | Basingstoke: Nature Publishing Group, 2014 |
Medientyp: | academicJournal |
Umfang: | print; 13; 1 p.1/4 |
ISSN: | 0893-133X (print) |
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