Intracerebroventricular Streptozotocin Exacerbates Alzheimer-Like Changes of 3xTg-AD Mice

被引:91
作者
Chen, Yanxing [1 ,2 ,3 ]
Liang, Zhihou [3 ]
Tian, Zhu [1 ,4 ]
Blanchard, Julie [1 ]
Dai, Chun-ling [1 ]
Chalbot, Sonia [1 ]
Iqbal, Khalid [1 ]
Liu, Fei [1 ]
Gong, Cheng-Xin [1 ]
机构
[1] New York State Inst Basic Res Dev Disabil, Dept Neurochem, Staten Isl, NY 10314 USA
[2] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou 310009, Zhejiang, Peoples R China
[3] Huazhong Univ Sci & Technol, Dept Neurol, Union Hosp, Tongji Med Coll, Wuhan 430022, Hubei, Peoples R China
[4] Tianjin First Ctr Hosp, Dept Neurol, Tianjin 300192, Peoples R China
基金
美国国家卫生研究院;
关键词
Streptozotocin; 3xTg-AD mice; Cognitive deficits; Tau phosphorylation; Amyloid-beta; Synaptic proteins; Neuroinflammation; Insulin signaling; OBJECT RECOGNITION MEMORY; TRIPLE-TRANSGENIC MODEL; A-BETA; INSULIN-RESISTANCE; TAU-HYPERPHOSPHORYLATION; GLUCOSE TRANSPORTERS; ENERGY-METABOLISM; AMYLOID-BETA; SYNAPSE LOSS; RAT-BRAIN;
D O I
10.1007/s12035-013-8539-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Alzheimer's disease (AD) involves several possible molecular mechanisms, including impaired brain insulin signaling and glucose metabolism. To investigate the role of metabolic insults in AD, we injected streptozotocin (STZ), a diabetogenic compound if used in the periphery, into the lateral ventricle of the 6-month-old 3xTg-AD mice and studied the cognitive function as well as AD-like brain abnormalities, such as tau phosphorylation and A beta accumulation, 3-6 weeks later. We found that STZ exacerbated impairment of short-term and spatial reference memory in 3xTg-AD mice. We also observed an increase in tau hyperphosphorylation and neuroinflammation, a disturbance of brain insulin signaling, and a decrease in synaptic plasticity and amyloid beta peptides in the brain after STZ treatment. The expression of 20 AD-related genes, including those involved in the processing of amyloid precursor protein, cytoskeleton, glucose metabolism, insulin signaling, synaptic function, protein kinases, and apoptosis, was altered, suggesting that STZ disturbs multiple metabolic and cell signaling pathways in the brain. These findings provide experimental evidence of the role of metabolic insult in AD.
引用
收藏
页码:547 / 562
页数:16
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