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Molecular Neurobiology

, Volume 49, Issue 1, pp 547–562 | Cite as

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

  • Yanxing Chen
  • Zhihou Liang
  • Zhu Tian
  • Julie Blanchard
  • Chun-ling Dai
  • Sonia Chalbot
  • Khalid Iqbal
  • Fei Liu
  • Cheng-Xin Gong
Article

Abstract

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 Aβ 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 β 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.

Keywords

Streptozotocin 3xTg-AD mice Cognitive deficits Tau phosphorylation Amyloid-β Synaptic proteins Neuroinflammation Insulin signaling 

Notes

Acknowledgements

We thank F.M. LaFerla of University of California, Irvine, for providing the breeding pairs of 3xTg-AD mouse, and Ms. J. Murphy for secretarial assistance. This work was supported in part by the New York State Office for People with Developmental Disabilities as well as grants from the National Institutes of Health (R01 AG027429 and R03 TW008123), the U.S. Alzheimer's Association (IIRG-10-170405 and IIRG-10-173154), the National Key Basic Research Program of China (2013CB530900), and the Wuhan Science and Technology Bureau, China (200960323132). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests

The authors declare that they have no competing interests.

Supplementary material

12035_2013_8539_MOESM1_ESM.docx (27 kb)
ESM 1 (DOCX 27 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Yanxing Chen
    • 1
    • 2
    • 3
  • Zhihou Liang
    • 3
  • Zhu Tian
    • 1
    • 4
  • Julie Blanchard
    • 1
  • Chun-ling Dai
    • 1
  • Sonia Chalbot
    • 1
  • Khalid Iqbal
    • 1
  • Fei Liu
    • 1
  • Cheng-Xin Gong
    • 1
  1. 1.Department of Neurochemistry, Inge Grundke-Iqbal Research FloorNew York State Institute for Basic Research in Developmental DisabilitiesStaten IslandUSA
  2. 2.Department of Neurology, the Second Affiliated Hospital, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Department of Neurology, Union Hospital, Tongji Medical CollegeHuazhong University of Science & TechnologyWuhanChina
  4. 4.Department of NeurologyTianjin First Center HospitalTianjinChina

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