Protective effects of 7,8-dihydroxyflavone on neuropathological and neurochemical changes in a mouse model of Alzheimer's disease.
Protective effects of 7,8-dihydroxyflavone on neuropathological and neurochemical changes in a mouse model of Alzheimer's disease.
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DOI：
10.1016/j.ejphar.2018.02.045
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发表时间：
2018-06-05
影响因子：
5
通讯作者：
Dedeoglu A
中科院分区：
文献类型：
--
作者：
Aytan N;Choi JK;Carreras I;Crabtree L;Nguyen B;Lehar M;Blusztajn JK;Jenkins BG;Dedeoglu A
脑源性神经营养因子(BDNF)在神经退行性疾病，特别是阿尔茨海默病(AD)中的表达降低，引起了人们的极大兴趣。BDNF信号通过TrkB受体在促进突触传递、突触发生和促进突触可塑性方面起着核心作用，使BDNF-TrkB信号通路成为靶向治疗的一个有吸引力的候选途径。在这里，我们研究了小分子TrkB激动剂7，8-二羟基黄酮(7，8-DHF)对5xFAD小鼠模型AD相关病理、树突分枝、突触密度和神经化学变化的早期影响。我们用7，8-DHF治疗5xFAD小鼠，从1个月龄开始用药2个月。我们发现，在这个AD模型中，7，8-DHF治疗减少了皮质Aβ斑块的沉积，并保护皮质神经元免受树突复杂性的影响，但对树突棘的密度没有显著影响。此外，7，8-DHF处理可抑制海马区胆碱类化合物水平的升高和谷氨酸的丢失，但对海马区神经发生无明显影响。
Interest in brain-derived neurotrophic factor (BDNF) was greatly enhanced when it was recognized that its expression is reduced in neurodegenerative disorders, especially in Alzheimer’s disease (AD). BDNF signaling through the TrkB receptor has a central role in promoting synaptic transmission, synaptogenesis, and facilitating synaptic plasticity making the BDNF-TrkB signaling pathway an attractive candidate for targeted therapies. Here we investigated the early effect of the small molecule TrkB agonist, 7,8 dihydroxyflavone (7,8-DHF), on AD-related pathology, dendritic arborization, synaptic density, and neurochemical changes in the 5xFAD mouse model of AD. We treated 5xFAD mice with 7,8-DHF for 2 months beginning at 1 month of age. We found that, in this model of AD, 7,8-DHF treatment decreased cortical Aβ plaque deposition and protected cortical neurons against reduced dendritic arbor complexity but had no significant impact on the density of dendritic spines. In addition 7,8-DHF treatment protected against hippocampal increase in the level of choline-containing compounds and glutamate loss, but had no significant impact on hippocampal neurogenesis.
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影响因子：
4.7
作者：
Choi, Ji-Kyung;Carreras, Isabel;Dedeoglu, Alpaslan;Jenkins, Bruce G.
通讯作者：
Jenkins, Bruce G.
影响因子：
3.7
作者：
Castello NA;Nguyen MH;Tran JD;Cheng D;Green KN;LaFerla FM
通讯作者：
LaFerla FM
7, 8-二羟基黄酮激活 TrkB 可增加突触 AMPA 亚基并改善阿尔茨海默病小鼠模型的空间记忆缺陷
影响因子：
4.7
作者：
Gao, Lei;Tian, Mi;Zeng, Yan
通讯作者：
Zeng, Yan
DOI：
10.1016/s0169-328x(97)00125-3
发表时间：
1997-10-03
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Connor, B;Young, D;Dragunow, M
通讯作者：
Dragunow, M
影响因子：
3.5
作者：
Garcia-Diaz Barriga, Gerardo;Giralt, Albert;Alberch, Jordi
通讯作者：
Alberch, Jordi