Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
Neuroprotective effects of brain-derived neurotrophic factor in rodent and primate models of Alzheimer's disease.
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DOI：
10.1038/nm.1912
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发表时间：
2009-03
期刊：
影响因子：
82.9
通讯作者：
Tuszynski MH
中科院分区：
文献类型：
--
作者：
Nagahara AH;Merrill DA;Coppola G;Tsukada S;Schroeder BE;Shaked GM;Wang L;Blesch A;Kim A;Conner JM;Rockenstein E;Chao MV;Koo EH;Geschwind D;Masliah E;Chiba AA;Tuszynski MH
内嗅皮层神经元功能紊乱导致阿尔茨海默病患者短期记忆早期丧失。在这里，我们显示了广泛的神经保护作用的内嗅脑源性神经营养因子（BDNF）管理在几个动物模型的阿尔茨海默氏病，与扩展的治疗效益到退化的海马。在淀粉样蛋白转基因小鼠中，当在疾病发作后给予BDNF基因递送时，逆转突触丧失，部分正常化异常基因表达，改善细胞信号传导并恢复学习和记忆。这些结果的发生与对淀粉样斑块负荷的影响无关。在老年大鼠中，BDNF输注逆转了认知能力下降，改善了基因表达中与年龄相关的扰动，并恢复了细胞信号传导。在成年大鼠和灵长类动物中，BDNF可防止损伤诱导的内嗅皮层神经元死亡。在老年灵长类动物中，BDNF逆转神经元萎缩并改善与年龄相关的认知障碍。总的来说，这些发现表明BDNF对参与阿尔茨海默病的关键神经元回路发挥实质性的保护作用，通过淀粉样蛋白非依赖性机制发挥作用。脑源性神经营养因子的治疗传递值得探索作为一种潜在的治疗阿尔茨海默病。
Profound neuronal dysfunction in the entorhinal cortex contributes to early loss of short-term memory in Alzheimer’s disease. Here we show broad neuroprotective effects of entorhinal brain-derived neurotrophic factor (BDNF) administration in several animal models of Alzheimer’s disease, with extension of therapeutic benefits into the degenerating hippocampus. In amyloid-transgenic mice, BDNF gene delivery, when administered after disease onset, reverses synapse loss, partially normalizes aberrant gene expression, improves cell signaling and restores learning and memory. These outcomes occur independently of effects on amyloid plaque load. In aged rats, BDNF infusion reverses cognitive decline, improves age-related perturbations in gene expression and restores cell signaling. In adult rats and primates, BDNF prevents lesion-induced death of entorhinal cortical neurons. In aged primates, BDNF reverses neuronal atrophy and ameliorates age-related cognitive impairment. Collectively, these findings indicate that BDNF exerts substantial protective effects on crucial neuronal circuitry involved in Alzheimer’s disease, acting through amyloid-independent mechanisms. BDNF therapeutic delivery merits exploration as a potential therapy for Alzheimer’s disease.
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影响因子：
56.9
作者：
Kaspar, BK;Lladó, J;Gage, FH
通讯作者：
Gage, FH
影响因子：
82.9
作者：
Gill, SS;Patel, NK;Heywood, P
通讯作者：
Heywood, P
影响因子：
168.9
作者：
Kaplitt, Michael G.;Feigin, Andrew;During, Matthew J.
通讯作者：
During, Matthew J.
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
DOI：
10.1073/pnas.95.17.10235
发表时间：
1998-08-18
影响因子：
11.1
作者：
Levine, ES;Crozier, RA;Plummer, MR
通讯作者：
Plummer, MR