TY - JOUR
T1 - 7,8-Dihydroxyflavone improves memory consolidation processes in rats and mice
AU - Bollen, E.
AU - Vanmierlo, T.
AU - Akkerman, S.
AU - Wouters, C.
AU - Steinbusch, H. M. W.
AU - Prickaerts, J.
PY - 2013/11/15
Y1 - 2013/11/15
N2 - 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.
AB - 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.
KW - Brain-derived neurotrophic factor
KW - TrkB receptor
KW - 7,8-Dihydroxyflavone
KW - Memory consolidation
KW - Alzheimer's disease
KW - Cognition enhancers
U2 - 10.1016/j.bbr.2013.09.029
DO - 10.1016/j.bbr.2013.09.029
M3 - Article
C2 - 24070857
SN - 0166-4328
VL - 257
SP - 8
EP - 12
JO - Behavioural Brain Research
JF - Behavioural Brain Research
ER -