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Journal of Neural Transmission

, Volume 119, Issue 11, pp 1407–1416 | Cite as

Changes in insulin-signaling transduction pathway underlie learning/memory deficits in an Alzheimer’s disease rat model

  • Xiaojuan Han
  • Yan Ma
  • Xiaohui Liu
  • Lu Wang
  • Shen Qi
  • Qinghua Zhang
  • Yifeng DuEmail author
Dementias - Original Article

Abstract

Brain metabolic dysregulation is a hallmark pathological change in Alzheimer’s disease (AD). Although detailed mechanisms are still not fully elucidated, recent studies suggest alterations of insulin-signaling transduction cascades underlie neuronal stresses in AD brains. In this study, we performed in vivo experiments to determine the impact of soluble Aβ oligomers on insulin-signaling transduction in rat hippocampi by utilizing lateral ventricular injection of amyloid beta (Aβ) oligomers on male Wistar rats (225 ± 25 g, 3–4 months old) as an AD rat model. The Aβ-infused rats manifested remarkably increased escape latency and significantly decreased proportions of time and pathway crossing the hidden platform as compared to the rats in the pseudo-injection group and the non-injection group in Morris water maze test implicating the damaging effect of soluble Aβ oligomers on rat learning and memory functions. Accordingly, our subsequent results demonstrated that the infusion of soluble Aβ oligomers significantly decreased the expressions of insulin receptor, insulin receptor substrate-I, B cell lymphoma/leukemia-2 and serine/threonine protein kinase B in rat hippocampal neurons, whereas the expression level of total cAMP response element-binding protein was not changed. This study suggests that soluble Aβ oligomers instigated insulin-signaling disturbances which are potentially associated with learning and memory deficits in the AD rat model.

Keywords

Alzheimer’s disease Soluble Aβ oligomers Insulin-signaling transduction pathway Rats 

Notes

Acknowledgments

This study was supported by the Natural Science Foundation of Shandong Province (Y2008C116). We thank Dr. Edward C. Mignot for linguistic advice and Professor Shuli Sheng and Heng Du for revisal advice.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Xiaojuan Han
    • 1
  • Yan Ma
    • 2
  • Xiaohui Liu
    • 1
  • Lu Wang
    • 1
  • Shen Qi
    • 1
  • Qinghua Zhang
    • 1
  • Yifeng Du
    • 1
    Email author
  1. 1.Department of NeurologyProvincial Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China
  2. 2.Department of NeurologyNo. 1 Central Hospital of Bao Ding CityBaodingPeople’s Republic of China

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