1. 7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice
- Author
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Harry Steinbusch, Jos Prickaerts, Tim Vanmierlo, Sven Akkerman, Eva Bollen, Carine Wouters, Psychiatrie & Neuropsychologie, and RS: MHeNs School for Mental Health and Neuroscience
- Subjects
Male ,TrkB receptor ,Mice, Transgenic ,Tropomyosin receptor kinase B ,CREB ,7,8-Dihydroxyflavone ,Brain-derived neurotrophic factor ,Amyloid beta-Protein Precursor ,Mice ,Behavioral Neuroscience ,Alzheimer Disease ,Neurotrophic factors ,Memory improvement ,Presenilin-1 ,Animals ,Humans ,Receptor, trkB ,Rats, Wistar ,Maze Learning ,Memory consolidation ,Memory Disorders ,biology ,virus diseases ,Recognition, Psychology ,Long-term potentiation ,Alzheimer's disease ,8-Dihydroxyflavone ,Rats ,Cognition enhancers ,Mice, Inbred C57BL ,Disease Models, Animal ,Flavanones ,Mutation ,Exploratory Behavior ,biology.protein ,Psychology ,Neuroscience - Abstract
Brain-derived neurotrophic factor (BDNF) is a crucial regulator of neuronal survival and neuroplasticity in the central nervous system (CNS). As a result, there has been a growing interest in the role of BDNF in neuropsychiatric disorders associated with neurodegeneration, including depression and dementia. However, until now, BDNF-targeting therapies have yielded disappointing results. BDNF is thought to exert its beneficial effects on synaptic and neuronal plasticity mainly through binding to the tyrosine kinase B (TrkB) receptor. Recently, 7,8-dihydroxyflavone (7,8-DHF) was identified as the first selective TrkB agonist. In the present study the effect of 7,8-DHF on memory consolidation processes was evaluated. In healthy rats, 7,8-DHF improved object memory formation in the object recognition task when administered both immediately and 3 h after learning. In a transgenic mouse model of Alzheimer's disease, i.e. APPswe/PS1dE9 mice, spatial memory as measured in the object location task was improved after administration of 7,8-DHF. A similar memory improvement was found when their wild-type littermates were treated with 7,8-DHF. The acute beneficial effects in healthy mice suggest that effects might be symptomatic rather than curing. Nevertheless, this study suggests that 7,8-DHF might be a promising therapeutic target for dementia. more...
- Published
- 2013
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