7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice.
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 3h 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.
Department of Psychiatry and Neuropsychology, School of Mental Health and Neuroscience, Maastricht University, The Netherlands.
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E
Bollen
T
T
Vanmierlo
S
S
Akkerman
C
C
Wouters
H M W
HM
Steinbusch
J
J
Prickaerts
D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects; D044950:Flavanones / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000819:agonists*; D021641:Recognition, Psychology / Q000187:drug effects
C478869:7,8-dihydroxyflavanone; D016564:Amyloid beta-Protein Precursor; D044950:Flavanones; C508853:PSEN1 protein, human; D053764:Presenilin-1; D020813:Receptor, trkB
7,8-DHF; 7,8-Dihydroxyflavone; 7,8-dihydroxyflavone; AD; Alzheimer's disease; Aβ; BDNF; Brain-derived neurotrophic factor; CNS; CREB; Ca(2+)/calmodulin-dependent protein kinase II; CaMKII; Cognition enhancers; LTP; Memory consolidation; N-methyl-d-aspartic acid; NMDA; OLT; ORT; PTSD; T1; T2; TrkB; TrkB receptor; WT; amyloid beta; brain-derived neurotrophic factor; cAMP-responsive element binding; central nervous system; first trial; i.p.; intraperitoneal; long-term potentiation; mBDNF; mature BDNF; object location task; object recognition task; p.o.; per os; post-traumatic stress disorder; precursor of BDNF; proBDNF; second trial; tyrosine kinase B; wild-type