PMID- 22710915
OWN - NLM
STAT- MEDLINE
DCOM- 20130708
LR  - 20120912
IS  - 1875-8908 (Electronic)
IS  - 1387-2877 (Linking)
VI  - 31
IP  - 4
DP  - 2012
TI  - Activation of TrkB by 7,8-dihydroxyflavone prevents fear memory defects and 
      facilitates amygdalar synaptic plasticity in aging.
PG  - 765-78
LID - 10.3233/JAD-2012-120886 [doi]
AB  - 7,8-dihydroxyflavone (7,8-DHF) has recently been identified as a brain-derived 
      neurotrophic factor (BDNF) mimetic to selectively activate the 
      tropomyosin-related kinase B (TrkB) with high affinity. We have previously 
      demonstrated that 7,8-DHF in vitro rescues long-term synaptic plasticity in the 
      hippocampus of aged rats. The present study assessed the effectiveness of 7,8-DHF 
      on age-related declines in fear memories and amygdalar synaptic plasticity. We 
      found that Sprague Dawley male rats began to show significant deficits in the 
      acquisition and retention of memories for contextual and cued fear conditioning, 
      as well as the reduction of BDNF, TrkB, and phosphorylated TrkB at the age of 25 
      months. Therefore, rats at 24 months old received intraperitoneal administration 
      of either 7,8-DHF (5 mg/kg, i.p.) or vehicle once daily for a consecutive 4 
      weeks. At the end of treatment period, cognitive performance, amygdalar synaptic 
      plasticity, synaptogenesis, and the phosphorylation of several proteins crucial 
      to synaptic plasticity were evaluated. The results show that chronic 7,8-DHF 
      treatments significantly enhanced the activation of phosphorylated TrkB at the 
      Y515 and Y816 sites, increased spine density and number in several brain regions 
      that process fear memory including the amygdala, hippocampus, and prefrontal 
      cortex, facilitated basolateral amygdalar synaptic plasticity, and in turn 
      prevented performance in fear conditioning tasks from declining. Our results thus 
      confirm a critical role for TrkB signaling activation by 7,8-DHF in preventing 
      age-related declines in fear learning and memory and strongly suggest a potential 
      usefulness for 7,8-DHF or a TrkB agonist in reversing age-related memory 
      impairment.
FAU - Zeng, Yan
AU  - Zeng Y
AD  - Department of Pathophysiology, School of Medicine, Wuhan University of Science 
      and Technology, Wuhan, Hubei, PR China. yanzeng11@yahoo.com
FAU - Liu, Yakun
AU  - Liu Y
FAU - Wu, Mianyun
AU  - Wu M
FAU - Liu, Jun
AU  - Liu J
FAU - Hu, Qi
AU  - Hu Q
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - J Alzheimers Dis
JT  - Journal of Alzheimer's disease : JAD
JID - 9814863
RN  - 0 (6,7-dihydroxyflavone)
RN  - 0 (Flavones)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Aging/drug effects/*metabolism
MH  - Amygdala/drug effects/*enzymology
MH  - Animals
MH  - Enzyme Activation/drug effects/physiology
MH  - Fear/drug effects/*physiology
MH  - Flavones/*pharmacology/therapeutic use
MH  - Male
MH  - Memory Disorders/enzymology/*prevention & control
MH  - Neuronal Plasticity/drug effects/physiology
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Organ Culture Techniques
MH  - Phosphorylation/drug effects/physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/*metabolism/physiology
MH  - Synapses/drug effects/enzymology
EDAT- 2012/06/20 06:00
MHDA- 2013/07/09 06:00
CRDT- 2012/06/20 06:00
PHST- 2012/06/20 06:00 [entrez]
PHST- 2012/06/20 06:00 [pubmed]
PHST- 2013/07/09 06:00 [medline]
AID - A727730627Q72G57 [pii]
AID - 10.3233/JAD-2012-120886 [doi]
PST - ppublish
SO  - J Alzheimers Dis. 2012;31(4):765-78. doi: 10.3233/JAD-2012-120886.