期刊
NEUROPSYCHOPHARMACOLOGY
卷 39, 期 3, 页码 638-650出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2013.243
关键词
7,8-Dihydroxyflavone; Synapse; TrkB; Alzheimer's disease; neuroprotection
资金
- National Institute of Health [RO1, DC010204]
- NIH/NIAP50 ADRC center grant
- National Natural Science Foundation of China [81100958]
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 A beta-induced toxicity and promoted dendrite branching and synaptogenesis. Chronic oral administration of 7,8-DHF activated TrkB signaling and prevented Ab 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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